Konjac Glucomannan as a Gel-Forming Biopolymer for Transdermal Drug Delivery: Properties, Formulation Strategies, and Translational Challenges

Abstract

Konjac glucomannan is a natural polysaccharide increasingly relevant as a matrix forming material for skin applied delivery systems. Its potential is linked to its glucose and mannose backbone, abundant hydroxyl groups, partial acetyl substitution, high molecular weight, and capacity for chain association. These features regulate hydration, swelling, rheology, viscoelasticity, film formation, gelation, and drug release. This narrative review examines konjac glucomannan from a structure based formulation perspective, covering physicochemical attributes, modification strategies, formulation platforms, release behavior, and evaluation requirements. Unlike previous reviews that broadly discuss polysaccharide based transdermal systems or glucomannan across pharmaceutical applications, this review focuses on the relationship between KGM structure, formulation design, and translational performance. Evidence shows its use in films, hydrogel reservoirs, injectable hydrogels, nanofibrous systems, carrier assisted systems, and multilayer matrices. In these platforms, konjac glucomannan functions as a hydration regulating matrix former, release modulator, and structural component. Blending, deacetylation, oxidation, crosslinking, freeze thaw treatment, electrospinning, and layered design can improve mechanical integrity, moisture control, and release performance. However, outcomes vary with molecular attributes, modification conditions, and evaluation methods. Most studies remain focused on material characterization and in vitro release, while durable skin adhesion, ex vivo permeation, skin deposition, long wear performance, and clinically meaningful transport are still insufficiently demonstrated. Further translation requires standardized molecular attributes, ex vivo and in vivo testing, scalable manufacturing, and regulatory evaluation.

Introduction

Konjac glucomannan (KGM) is a naturally derived polysaccharide that has long been used in food, material, and pharmaceutical applications because of its high water affinity, thickening ability, gel-forming behavior, and generally favorable safety profile.1,2 Beyond its widespread use in the food sector, KGM has also been explored in porous materials, packaging films, wound dressings, and controlled release systems, indicating that it is not merely an experimental polymer but a functionally versatile and scalable biomaterial.2,3 The broad application landscape of KGM across food, material, and pharmaceutical fields is summarized in Figure 1, which helps explain why this polysaccharide has attracted increasing interest as a candidate.

Figure 1.

Broad application landscape of konjac glucomannan across food, material, and pharmaceutical fields (Created in BioRender. Sriwidodo, S (2026) https://BioRender.com/jr7wnxt).

In pharmaceutics, the interest in KGM has gradually expanded from its traditional role as a thickener or supportive excipient toward a more active matrix forming component in advanced dosage forms.1 Structurally, KGM is a non ionic high molecular weight polysaccharide composed of D-glucose and D-mannose linked through β-(1→4) glycosidic bonds, with a glucose to mannose ratio commonly reported in the range of 1:1.4–1.74,5 or 1:2–3.6 Acetyl groups are distributed along the chain, mainly at the C-6 position, and are usually present at approximately one acetyl group per 9 to 20 sugar residues.3 These structural characteristics are closely related to its hydration behavior, viscoelasticity, and ability to form coherent soft matrices, which explains why KGM has become attractive in formulations requiring sustained water retention, controlled swelling, and adaptable network formation.7–9

These properties are particularly relevant to transdermal drug delivery systems (TDDS). Compared with conventional oral administration, TDDS avoids first pass hepatic metabolism and may improve the bioavailability of suitable drug candidates.10 It also offers non invasive and painless administration, supports both local and systemic delivery, and allows rapid termination of dosing simply by removing the patch from the skin surface.10 However, the major limitation of TDDS remains the skin barrier, especially the stratum corneum, which restricts passive transport and often results in low flux and prolonged lag time.11–13 Because its dense lipid organization generally favors only compounds with low molecular weight and moderate lipophilicity, many therapeutically useful molecules require formulation based assistance to cross the skin effectively.10,14

From this perspective, KGM is relevant to TDDS not because it can independently overcome the skin barrier, but because it can fulfill several matrix level requirements that are important for transdermal formulation design. Its strong hydration behavior may help maintain close interfacial contact with the skin, while its gel-forming and film-forming capacity makes it suitable for constructing soft matrices capable of sustained release.15,16 At the same time, native KGM is not automatically ideal for TDDS, since its gel network may be mechanically fragile, highly moisture sensitive, and prone to rapid drug diffusion or burst release when insufficiently reinforced.17 These limitations explain why KGM is more often explored in composite, modified, or structurally engineered forms than as a stand alone polymer in advanced skin applied delivery system.

Compared with other commonly investigated polymers, KGM offers a distinct balance of hydration and matrix forming properties. Chitosan provides cationic charge, film formation, bioadhesion, and potential permeation enhancement, although its solubility is pH dependent.18 Alginate forms hydrogels under mild ionic crosslinking and is widely used in wound and transdermal systems, but its gel strength and stability depend on composition and crosslinking conditions.19,20 Hyaluronic acid supports skin hydration and compatibility, whereas cellulose derivatives provide established film-forming, viscosity modifying, and bioadhesive functions.21–23 KGM should therefore be viewed as complementary rather than universally superior. Its main value lies in hydration, swelling, and gel formation, while high viscosity and limited mechanical strength in some formulations remain relevant limitations.2,3

Recent studies have expanded KGM formulation design toward composite hydrogels, nanofiber membranes, and skin-contact films. KGM/oxidized hyaluronic acid hydrogels, carboxymethyl KGM/gelatin hydrogels, KGM based nanofiber membranes, and drug loaded KGM composite hydrogels have been investigated to improve swelling, mechanical properties, and controlled release. KGM and Chitosan/KGM films containing active compounds have also shown properties relevant to skin contact application. However, these studies often remain focused on material characterization, model medium release, or wound related outcomes rather than direct evidence of drug transport across skin.

Although natural polysaccharides have already been discussed in broader TDDS reviews,14,24 and KGM has been considered in broader pharmaceutical and wound dressing contexts, a focused and critical synthesis of KGM as a gel-forming functional excipient for transdermal delivery remains limited.10,14 Accordingly, this review examines KGM in relation to its structural and physicochemical basis, modification strategies, formulation platforms, evaluation approaches, and current level of transdermal relevance. By doing so, it aims to clarify how the long standing industrial and pharmaceutical utility of KGM can be translated more rationally into next generation transdermal systems, with particular emphasis on the relationship between KGM structure, formulation design, and clinically relevant transdermal performance.

Methods

This article was designed as a structured narrative review to critically synthesize the role of konjac glucomannan as a matrix forming biopolymer for skin applied and transdermal drug delivery systems. The review was not intended to perform a systematic review, meta analysis, or quantitative comparison of formulation performance. Instead, it aimed to clarify the relationship between molecular structure, material attributes, formulation strategy, and translational relevance. The scope was organized into five main domains: structural and physicochemical characteristics, modification strategies, formulation platforms, drug loading and release behavior, and evaluation requirements for skin relevant systems.

A targeted literature search was conducted using PubMed, Scopus, Web of Science, and ScienceDirect for articles published between 2017–2026. Search terms included combinations of konjac glucomannan, glucomannan, KGM, acetylation, deacetylation, molecular weight, hydration, swelling, rheology, gelation, hydrogel, crosslinking, transdermal drug delivery, topical delivery, skin permeation, and drug release. Additional articles were identified from the reference lists of relevant studies and reviews. Peer reviewed research articles, review papers, and selected methodological studies were considered when they provided information relevant to KGM structure, matrix behavior, formulation design, release control, or skin related delivery performance.

Because direct transdermal evidence for KGM remains limited, the literature was interpreted conservatively. Studies with direct relevance to skin applied or transdermal systems were prioritized, while selected non transdermal KGM studies were included only when their material findings were transferable to matrix design, such as moisture regulation, mechanical reinforcement, viscoelasticity, and controlled release. The synthesis was thematic rather than statistical, and formal PRISMA screening was not performed.

Structure and Key Material Attributes of Glucomannan

Konjac glucomannan (KGM) is a naturally derived polysaccharide obtained mainly from the tubers of Amorphophallus konjac, a source long associated with food, biomedical, and pharmaceutical applications because of its availability, biocompatibility, and strong hydration capacity.1,2,25 Its growing relevance in transdermal formulation does not stem merely from its natural origin, but from the fact that it combines water affinity, film and gel-forming ability, and broad compatibility with co-polymers commonly used in functional matrices.3,16,26 In this context, KGM should be viewed not simply as a passive excipient, but as a structurally responsive material whose molecular features directly influence matrix behavior.3,26

Structurally, KGM is a non ionic heteropolysaccharide composed of D-mannose and D-glucose residues linked predominantly through β-(1→4) glycosidic bonds.5,6 The reported monosaccharide ratio varies across studies, with glucose:mannose values commonly described as 1:1.4–1.7 or 1:2–3, whereas other reports express the composition as a mannose:glucose ratio of approximately 1:1.5 to 1:1.6.4,27 Although these numerical differences may appear modest, they are functionally relevant because the mannose and glucose balance affects hydration, intermolecular packing, and the tendency of the chains to associate during film or gel formation.4,6,27 KGM is generally regarded as predominantly linear, although limited branching, including occasional β-(1→3) linkages on mannose residues, has also been reported.27 This largely linear architecture favors chain entanglement and contributes to the formation of cohesive hydrated networks, while its semi-crystalline tendency helps explain how KGM can remain highly hydrophilic yet still form organized gel like structures under suitable conditions.28

A defining structural feature of KGM is the presence of acetyl substituents distributed along the chain, mainly at the C-6 position of sugar residues.3,29 Native KGM commonly contains acetyl groups on about 5–10% of its sugar units, corresponding broadly to one acetyl group for every 9–20 monosaccharide residues.30 This degree of substitution is sufficient to influence polymer behavior substantially, because acetyl groups improve cold water solubility and preserve chain flexibility by limiting excessive interchain hydrogen bonding.29,31 When acetyl content decreases, chain association becomes stronger and the network tends to become denser, less swellable, and mechanically stiffer.32,33 Recent primary evidence supports this interpretation. L-arginine mediated deacetylation generated KGM samples with deacetylation degrees of 17.51%, 35.41%, and 54.52%, while solubility decreased from 85.38% to 81.17% and transparency from 38.52% to 35.73%, indicating progressive restructuring of the hydrated polymer state.34 A separate study reported that deacetylated KGM aggregates with a deacetylation degree of 27.26% showed stronger self association and altered interfacial behavior, suggesting that moderate deacetylation can shift the balance between dispersibility and network compactness rather than simply making the material more rigid.35

Molecular weight is another major determinant of KGM performance. Reported values commonly range from 200 to 2000 kDa or from 500 to 2000 kDa, depending on source and processing history.36,37 Native KGM has also been reported at approximately 1.8×10⁶ Da, whereas enzymatically hydrolyzed material decreased to around 0.45×10⁶ Da, illustrating how strongly downstream handling can reshape the polymer.38 High molecular weight generally favors viscosity development, chain entanglement, and matrix coherence, whereas lower molecular weight improves dispersibility and processability but often weakens viscoelasticity and mechanical strength.36,38,39 Recent work has further reinforced this relationship. In mixed starch systems, higher molecular weight KGM increased viscosity and viscoelastic response, while in protein based gels it improved gel retention during storage, confirming that chain size remains a key driver of bulk material behavior even in multicomponent matrices.40,41

Taken together, these features indicate that KGM should be understood as a structurally variable material rather than a chemically fixed excipient. Differences in cultivar, extraction route, purification, storage, and processing can alter molecular weight, acetylation profile, and impurity burden, all of which influence the final physicochemical behavior.37,42,43 This is particularly relevant to transdermal formulation, where relatively small changes in viscosity, swelling, or gel coherence may translate into substantial differences in processing and performance.

To anchor the discussion that follows, the core molecular architecture of KGMis illustrated in Figure 2. Building on this molecular view, Figure 3 summarizes how these structural features translate into the key material attributes of KGM and into practical implications for hydrated matrix formation, release behavior, and platform design in skin applied systems.

Figure 2.

Core structural features of konjac glucomannan relevant to matrix behavior (Created in BioRender. Sriwidodo, S (2026) https://BioRender.com/345fqyt).

Figure 3.

Translation of KGM structural features into key material attributes and formulation implications relevant to transdermal design (Created in BioRender. Sriwidodo, S (2026) https://BioRender.com/mkbra21).

Key Material Attributes Derived from KGM Structure

The strong hydrophilicity of KGM arises from its hydroxyl rich backbone and is moderated by partial acetylation, which together promote rapid hydration and stable aqueous dispersion.31,44 This is one reason KGM is frequently considered suitable for film and hydrogel matrices intended for skin contact systems.16,25,26 The same feature, however, also explains why native KGM may become overly soft or unstable after water uptake when the network is not sufficiently reinforced.45

Swelling is one of the clearest manifestations of this structural behavior. In a highly KGM rich chitosan/KGM film, swelling reached 546% within 15 min, showing how rapidly the polymer can expand after hydration.46 In resveratrol modified chitosan/KGM films, swelling was reported at 581% at pH 7.4, whereas lower values were observed under acidic conditions because the interaction between matrix components changed with the medium.30 In oxidized hyaluronic acid/KGM hydrogels, increasing crosslink density reduced swelling, although local porosity could partially reverse that trend at selected compositions.45 These results show that swelling in KGM systems is structurally rooted but still strongly formulation dependent.

Water retention is closely related to swelling, but its importance lies in the capacity of the matrix to preserve local hydration over time.17,45 For transdermal systems, this may be advantageous because a moist interface can soften the stratum corneum and improve matrix skin contact. At the same time, excessive water retention may promote syneresis, film distortion, or storage instability when the network lacks sufficient cohesion.17,45 KGM solutions also typically show pseudoplastic or shear thinning behavior, meaning that viscosity decreases as shear rate increases.36 This rheological behavior is particularly relevant in pharmaceutical processing because it governs casting, coating, spreading, and, in more advanced systems, electrospinning.36,38

Viscoelasticity provides a more direct measure of whether the hydrated system behaves as a coherent gel. In many engineered KGM systems, the storage modulus (G′) exceeds the loss modulus (G″), indicating a solid like viscoelastic network.47,48 Oxidized KGM/chitosan hydrogels formed through Schiff-base chemistry exhibit G′ > G″ and show self healing behavior, suggesting the presence of recoverable dynamic junctions within the network.47 KGM/EGCG hydrogels similarly display elastic behavior, with modulus increasing as additional hydrogen bonding interactions reinforce the matrix.48 More recent work on deacetylated KGM/calcium alginate films showed that wet tensile strength rose to 2.896 MPa at a deacetylation degree of 53.77% but declined to 1.541 MPa at 83.34%, indicating that network strengthening is beneficial only up to an optimum level rather than increasing indefinitely.49

KGM also possesses strong film and gel-forming capacity because hydrogen bonding, chain entanglement, and physical or chemical crosslinking can all contribute to network construction.47,48,50,51 Freeze-thaw treatment is one example of physical structuring that can increase crystallinity and strengthen the resulting gel, although excessive crystallization may compromise flexibility.50 In κ-carrageenan/KGM double network hydrogels, compressive strength and modulus were 10–20 times higher than those of single network systems, demonstrating how structural reinforcement can markedly expand the usable mechanical window of KGM based matrices.51 Chemical modification offers a similar route to network strengthening. Dialdehyde starch-modified konjac flour films achieved tensile strength up to 33 MPa with a water contact angle of 87°, indicating simultaneous improvement in mechanical stability and surface barrier behavior.52 More recent reinforced KGM films containing bacterial cellulose and tea polyphenols reached tensile strength as high as 62.87 MPa with elongation at break of 38.17%, showing that native KGM can be transformed into a far more robust material when its network architecture is deliberately engineered.53

To clarify how these structural features translate into practical matrix behavior, the major structure attribute relationships relevant to transdermal design are summarized in Table 1.

Table 1.

Key Structural Features of Konjac Glucomannan and Their Functional Implications

Structural Feature	Mainly Affects	Transdermal Relevance	Ref.
Mannose rich β-(1→4)-linked backbone	Hydrophilicity, hydrogen bonding, matrix formation	Supports hydrated film and hydrogel formation	[4–6]
Abundant hydroxyl groups	Water binding and swelling	Improves skin hydration and matrix–skin contact, but may increase burst release risk	[31,44,46]
Partial acetylation	Solubility, chain flexibility, hydration	Favors soft hydrated matrices and improves aqueous processability	[37,54,55]
Reduced acetylation (deacetylation)	Network compactness, intermolecular association, mechanical strength	Improves dimensional stability and release control, although excessive deacetylation may reduce flexibility	[49,56,57]
High molecular weight	Viscosity, entanglement, gel coherence	Enhances matrix integrity but may complicate casting and processing	[36–38]
Molecular weight distribution	Rheological uniformity, network consistency	Influences formulation reproducibility and performance stability	[42,43,58]
Semicrystalline tendency	Structural organization and gel coherence	Supports formation of organized gel like domains in hydrated systems	[27,28]

Gelation Behavior and Relevance to Matrix Design

Gelation in KGM is governed primarily by non covalent interactions, especially hydrogen bonding and hydrophobic association among hydrated chains.59–61 The process is often described as thermoreversible, with heating increasing chain mobility and cooling facilitating the formation of an interconnected three dimensional network that traps water and produces an elastic gel.60 The degree of acetylation influences this process directly because acetyl groups promote solubility and flexibility but also interfere with strong chain–chain association.62 Highly acetylated KGM therefore tends to form weaker and more soluble gels, whereas partial deacetylation usually yields stronger and more stable networks through enhanced hydrogen bonding.63–65

Additional strengthening can be introduced through ionic or covalent crosslinking. Divalent ions such as Ca²⁺, Ba²⁺, and borate can act as intermolecular bridges and improve gel rigidity and structural integrity.66 Oxidation followed by dynamic or covalent bond formation can produce even stronger networks and, in some cases, self healing behavior.47,67 Chemical gelation usually leads to higher modulus, lower swelling, and more regulated release, but it also requires careful assessment of crosslinker safety if the final system is intended for prolonged skin contact.17,66,68

From a formulation perspective, the central implication is that KGM should not be regarded as a passive hydrocolloid. Its transdermal relevance depends on how backbone composition,58 degree of acetylation,69 and molecular weight70 characteristics translate into hydration, swelling, rheology, and gel coherence under real processing conditions.71,72 These same variables determine whether KGM behaves as a rapidly softening hydrophilic film, a stable hydrogel reservoir, or a mechanically reinforced matrix capable of supporting more controlled transdermal performance.10,73

Functional Requirements in Transdermal Drug Delivery and the Position of Glucomannan

Biological Barriers of the Skin

An effective transdermal drug delivery system must first overcome the intrinsic complexity of the skin as a biological barrier. Among all skin layers, the stratum corneum remains the principal determinant of percutaneous transport because it is organized as corneocytes embedded in a highly ordered lipid matrix composed mainly of ceramides, cholesterol, and free fatty acids.74 This tightly packed lipid domain acts as the main diffusional barrier for both hydrophilic and lipophilic molecules, while structural proteins such as filaggrin, loricrin, involucrin, and corneodesmosin help preserve barrier cohesion and surface homeostasis.74,75 When these proteins are impaired, the barrier becomes more vulnerable, surface pH rises, hydration decreases, and susceptibility to irritation increases. Beneath the stratum corneum, the viable epidermis and dermis add further resistance through cellular junctions and extracellular structural components, making the overall transport pathway highly selective.76

Because of this architecture, only a limited range of drug molecules is suitable for passive transdermal absorption. In general, compounds with a molecular weight of 500 Da or less, moderate lipophilicity, and limited hydrogen bonding capacity show the greatest probability of crossing intact skin.76 By contrast, hydrophilic drugs and macromolecules often display low flux and prolonged lag time.76 This limitation is reflected in experimental data. In an ex vivo study using porcine ear skin, a PVA/PVP based patch delivered only 39.3% of BGP-15 across the skin, with a flux of 0.465 mg cm⁻² h⁻¹, while 9.2% of the dose remained within the tissue.77 Likewise, polymeric film patches without an additional permeation promoting strategy released only 65.5% of tramadol hydrochloride within 12 h across goat skin, illustrating that drug release from the matrix alone does not necessarily translate into efficient skin penetration.77

Skin permeability is also highly dynamic and depends on hydration level, pH, and barrier integrity. Increased hydration expands interlamellar spacing in the stratum corneum and lowers barrier resistance, whereas dry skin reduces molecular mobility and suppresses permeation.74,78 Experimental imaging studies have shown that the application of an occlusive PET film can rapidly increase stratum corneum hydration from about 28% to 50–58% within one minute, accompanied by measurable thickening of the outer skin layer.78 However, hydration alone is not always sufficient to guarantee therapeutically meaningful drug transport. For that reason, excipients in TDDS should not be viewed merely as inert drug holders. They must also function as matrix modifiers capable of regulating hydration, skin contact, and local diffusional conditions.

Critical Functional Requirements of Transdermal Matrices

Skin Adhesion

A transdermal system must remain attached to a dynamic surface exposed to movement, temperature fluctuation, and occasional moisture. Recent hydrogel studies illustrate the level of performance generally required. PEG-gallate adhesive hydrogels achieved skin adhesion of approximately 1348 ± 211 Pa, and optimization of galloyl content together with network mesh size enabled strong adhesion without completely restricting solute transport.79 In another system, incorporation of polydopamine into polyacrylamide doubled both shear and peel strength through catechol based interfacial interactions.80 Likewise, catechol modified Janus hydrogels coordinated with Fe³⁺ reached tensile strengths of about 410 kPa and interfacial adhesion energies above 550 J m⁻² while still allowing reversible attachment.81 These data indicate that modern TDDS materials are expected to combine robust adhesion with controlled removability rather than relying on simple stickiness alone.

Water Retention and Local Hydration Control

Hydration of the stratum corneum reduces lipid rigidity and promotes diffusion, so the matrix should maintain a moist microenvironment at the skin surface.78 However, excessive swelling may cause structural instability, early drug loss, or patch deformation. This balance is clearly seen in highly hydrophilic hydrogel systems. Sodium alginate/hydroxyethyl cellulose hydrogels displayed pronounced swelling because of hydroxyl and carboxylate rich chains, and increasing the HEC fraction further increased swelling and accelerated drug release, whereas higher crosslinker concentration reduced both effects.82 Freeze-cast PVA/cellulose nanofiber hydrogels, by contrast, limited over swelling while preserving useful strength, showing that network architecture can be used to decouple water uptake from mechanical collapse.72 Thus, the desired property is not maximal hydration itself, but controlled hydration compatible with dimensional stability.

Controlled Drug Release

One of the defining advantages of TDDS is the possibility of maintaining relatively steady drug exposure over time, thereby reducing peak to trough fluctuations and improving tolerability. To achieve this, the matrix must regulate diffusion and avoid burst release. Polyacrylamide/polydopamine hydrogels loaded with PLGA nanoparticles showed near zero order release and delivered 50.7% of vitamin E over 24 h.80 Likewise, sodium alginate/hydroxyethyl cellulose patches delivered neomycin according to a zero order profile, with polymer ratio and crosslink density directly controlling the release rate.82 These findings reinforce a key design principle: release control depends less on any single polymer than on how network density, swelling, and drug matrix interactions are tuned together.

Mechanical Strength and Flexibility

A patch or film must resist tearing during handling and wear, yet remain sufficiently flexible to conform to curved or mobile skin surfaces. This becomes especially important when the application site lies near joints or areas exposed to repeated deformation. Composite hydrogels reinforced with chitin nanowhiskers increased tensile strength from 5 kPa to 11.2 kPa and showed elongation at break around 145%, while anisotropic PVA/cellulose nanofiber hydrogels reached tensile stress up to 0.91 MPa with a Young’s modulus of 102 kPa, values close to mechanically relevant soft tissues.72,83 These data show that flexibility and strength must be co-optimized, because either excessive softness or excessive rigidity can compromise wear performance.

Physicochemical Stability

A useful TDDS matrix must remain stable not only during application but also during storage. Water loss may produce brittle films, whereas excessive water uptake may cause syneresis, deformation, or drug migration. Freeze–thaw experiments on glucomannan containing hydrogels have shown that repeated freezing can increase crystallinity and strengthen the network, but uncontrolled structural rearrangement may also worsen brittleness or heterogeneity.50 At the same time, high humidity can plasticize films and reduce dimensional stability.52 This means that an ideal transdermal matrix must exhibit not only favorable immediate performance, but also predictable behavior under realistic storage and handling conditions.

Relevance and Position of Glucomannan in TDDS

Within this framework, KGM occupies an interesting but still transitional position. At the structural level, KGM already possesses several attributes favorable for TDDS. Its high molecular weight, abundant hydroxyl groups, and partial acetylation support strong water binding, swelling, and matrix formation. These are desirable features for systems intended to hydrate the stratum corneum and maintain close contact with the skin. In practical terms, KGM rich matrices can retain large amounts of water and create moist polymer networks that support drug dispersion.30,46 This alone makes KGM more attractive than many rigid, poorly hydrating polymers when the target dosage form is a film or hydrogel in direct contact with the skin.

At the same time, native KGM does not yet satisfy all functional criteria required for a robust TDDS. Its strong hydrophilicity can lead to excessive swelling and rapid loss of structural integrity when the network is not sufficiently reinforced. In chitosan/KGM films, for example, KGM rich formulations showed swelling values approaching 946% within 15 min, which is favorable for hydration but potentially problematic for long duration dimensional stability.30 A more recent study on resveratrol containing chitosan/KGM films reported that the BR10 formulation reached 581% swelling at pH 7.4 and also showed improved wettability, confirming that KGM rich matrices remain highly water responsive even after functional modification.46 These findings support the view that KGM is intrinsically well suited for hydration driven skin application, but they also show why uncontrolled swelling remains a central formulation challenge.

Mechanical limitations are equally important. Pure or weakly structured KGM gels are often too fragile for stand alone patch applications. Reinforcement through blending is therefore not optional but functionally necessary. In PVA/KGM systems, tensile strength increased from 5.4 MPa to 10.6 MPa and elongation at break increased from 7.24% to 18.1%, clearly demonstrating that KGM becomes more viable when integrated into composite matrices.36 Recent rheological evidence shows that increasing KGM concentration strengthens viscoelastic behavior. In gelatinized canna starch/KGM mixtures, raising KGM from 0.3% to 1.2% increased both G′ and G″, and all systems remained elastic dominant (G′ > G″), with the effect becoming more pronounced at 0.9% and 1.2% KGM.84 These results indicate that concentration alone can shift KGM from a weak hydrated dispersion toward a more mechanically coherent gel, although not yet to a level sufficient for all patch applications.

Another important issue is adhesion. Native KGM lacks catechol, thiol, or other reactive functionalities commonly associated with durable wet skin adhesion. As a result, its long term attachment to skin remains limited unless other adhesive components are introduced. This helps explain why the most promising KGM systems reported so far are blends or chemically modified networks rather than single polymer films. Chitosan, PVA, protein based matrices, and other co-polymers are repeatedly used not only to improve mechanical strength, but also to reduce dissolution, regulate swelling, and improve surface characteristics relevant to skin contact.30,36,46 In this sense, KGM should be viewed less as a fully ready transdermal matrix and more as a highly tunable structural component within multicomponent systems.

Despite these limitations, the scientific position of KGM remains strong. It already satisfies several baseline requirements for hydration, matrix formation, and compatibility with composite design. What it lacks in native adhesion and toughness can, at least in principle, be compensated through deacetylation, blending, interpenetrating networks, dynamic covalent crosslinking, or incorporation of hydrophobic domains.50 The accumulated evidence therefore does not support dismissing KGM as inadequate. Rather, it supports a more precise conclusion: KGM is promising as a foundational gel-forming biopolymer, but it requires formulation engineering before it can function reliably in advanced TDDS.

This relationship between transdermal requirements and KGM performance is summarized visually in Figure 4, which links the major biological barrier functions of the skin with the corresponding material functions expected from a transdermal matrix and the specific contributions that KGM can provide.

Figure 4.

Functional requirements for transdermal drug delivery and the positioning of glucomannan as a matrix-forming biopolymer (Created in BioRender. Sriwidodo, S (2026) https://BioRender.com/wr58qko).

Modification and Optimization Strategies for Glucomannan Based Transdermal Systems

In KGM based transdermal systems, modification primarily functions as a design tool for matching matrix behavior to the demands of a specific dosage form and drug candidate. The central issue is not whether KGM can be modified, but which modification route is most appropriate for the dominant formulation problem. In practice, modification is used to regulate network compactness, moisture transport, mechanical persistence, interfacial behavior, and release control, all of which directly influence how the matrix performs during application and wear.85–88

The choice of strategy is therefore context dependent. A matrix developed for prolonged skin contact may prioritize dimensional stability and mechanical reinforcement, whereas a system intended for controlled release of a hydrophilic drug may require tighter diffusion control. Likewise, film based systems, hydrogel reservoirs, bilayer matrices, and fibrous architectures do not necessarily benefit from the same type of modification. For that reason, KGM modification should be interpreted within a formulation framework rather than as a generic material adjustment step.

The current literature indicates that the main modification routes for KGM can be grouped into non covalent blending, structural tuning through deacetylation or oxidation, architectural design such as bilayer organization, and process driven approaches including freeze-thaw structuring and electrospinning.73,89–91 Each route changes the matrix through a different mechanism and therefore addresses a different formulation priority. Some strategies are more useful for strengthening the hydrated network, others for moderating moisture transfer, improving structural recovery, or producing a more organized release pathway.

Because many available studies were developed in food film, preservation, or broader biomaterial contexts, the literature is most reliable when interpreted first at the level of matrix effect and only then translated into possible relevance for TDDS design. Accordingly, Table 2 summarizes the principal KGM modification strategies, their main design principles, the dominant material effects reported, and the conservative formulation implications that can be drawn from them. To complement that overview, Figure 5 presents a decision tree framework for selecting the most appropriate modification route according to the dominant limitation of the native KGM matrix.

Table 2.

Modification Strategies Applied to KGM and Their Conservative Implications for Transdermal Formulation Design

Components	Modification Strategy	Design Principle	Key Variable	Reported Matrix Level Effect	Implication for TDDS	Ref.
KGM/pectin + emulsion	Blending + emulsion incorporation	Pectin stabilizes dispersed droplets, while hydrogen bonding compacts the continuous matrix	Oil fraction; KGM:pectin ratio; droplet size	Lower WVP; higher tensile strength and elongation; higher contact angle	Useful for matrices requiring better moisture control and possible accommodation of lipophilic payloads	[85]
KGM + protein	Blending + orientation (shear/drawing)	Anisotropic fibrous organization reduces tortuosity and improves structural continuity	KGM:protein ratio; shear intensity; temperature; plasticizer	Higher tensile strength and modulus; lower WVP; elongation maintained; lower burst tendency	Relevant when stronger and more dimensionally stable films are desired	[86]
PVA/KGM + liposomes	Synthetic polymer blending + lipid carrier	Hydrogen bonding between PVA and KGM supports the matrix, while liposomes provide an additional reservoir	PVA:KGM ratio; liposome loading; pH; film thickness	Higher tensile strength; lower WVP; better control of release onset; pH responsiveness	Suitable for organized release systems, especially when secondary carriers are needed	[87]
KGM/κ-carrageenan + YDF	Blending + thermal/ionic control	κ-carrageenan helices and YDF modify mesh structure and water distribution	KGM:κ-CG:YDF ratio; K⁺/Na⁺ ions; temperature; thickness	Higher G′ and modulus; lower WVP; reduced burst tendency	Supports tighter hydrated matrices without direct chemical crosslinking	[88]
KGM + pea protein isolate	Blending + thermal co-gelation	Protein denaturation and polysaccharide interaction reinforce the hydrated network	PPI:KGM ratio; pH relative to pI; ionic strength; temperature/time	Higher tensile strength and modulus; lower WVP; reduced burst tendency	Useful when network strengthening is needed in soft, hydrated matrices	[89]
KGM + gluten	Non covalent blending + hydration control	Hydrogen bonding and excluded volume effects tighten the mesh	KGM:protein ratio; water/plasticizer content; mixing history; thickness	Higher tensile strength and modulus; lower WVP; reduced burst tendency	Relevant for improving cohesion and release regularity without extensive chemical modification	[92]
KGM + KOGM	Multi fraction blending	Oligomeric glucomannan fractions modify water binding and stabilize the network during storage	KGM:KOGM ratio; RH/temperature; water content; storage condition	More stable WVP/WVTR; lower drift; fewer microcracks	Potentially useful for improving storage robustness of KGM based films	[90]
KGM + curdlan/κ-carrageenan/alginate	Blending + oriented processing (HME)	Noncovalent co-gelation combined with oriented processing improves matrix organization	Component ratio; water content; shear and temperature; cooling; thickness	Higher tensile strength and modulus; lower WVP; reduced burst tendency	Supports fabrication of tougher matrices where architecture contributes to performance	[93]
KGM + walnut protein/gluten	Blending + orientation (HME)	Hydrogen bonding and hydration controlled fiber orientation strengthen the matrix	Water content; screw speed; temperature; component ratio; cooling	Higher tensile strength and modulus; lower WVP; reduced burst tendency	Useful when mechanical reinforcement and lower moisture transfer are needed	[91]
KGM + protein/polysaccharide blends	Blending + physical architecture	Hydrogen bonding and excluded volume effects regulate hydration and tighten the mesh	Blend ratio; shear/temperature; water content; cooling; thickness	Higher tensile strength and modulus; lower WVP; reduced burst tendency	Suggests a practical route to improve matrix integrity through compositional design	[94]
dKGM ± protein	Deacetylation + non covalent blending	Lower acetyl content increases hydrogen bonding and network compactness	Degree of deacetylation; pH; water content; dKGM:protein ratio; cooling	Higher tensile strength and modulus; lower WVP; reduced burst tendency	Appropriate when swelling control and stronger network formation are priorities	[29]
dKGM ± biopolymer	Deacetylation + non covalent blending	Increased water binding regulation and denser mesh improve structural stability	Degree of deacetylation; pH; storage condition; blend ratio	Higher tensile strength and modulus; lower WVP; reduced burst tendency; better stability	Useful when native KGM is too water sensitive or structurally unstable	[31]
KGM/XG composite	Composite blending	Synergistic helical organization and hydrogen bonding increase structural cohesion	KGM:XG ratio; mixing order; acetyl/pyruvate content; ions; RH	Higher G′ and tensile strength; lower WVP; reduced burst tendency; longer lag behavior	Relevant when slower onset and more controlled transport are desired	[95]
KGM with tuned degree of acetylation	DA tuning + physical compensation	Lower acetylation tightens the mesh, while bilayer/PEC design compensates for handling properties	Target DA; plasticizer; blending; bilayer/PEC design	Higher tensile strength/modulus; lower WVP; longer lag behavior	Useful for reducing abrupt release and improving dimensional stability	[96]
KGM/CS bilayer + β-CD@OEO	PEC bilayer + host–guest design	Oppositely charged layers create functional separation, while β-CD hosts essential oil	CS:KGM ratio; β-CD@OEO content; layer thickness	Higher tensile strength; lower WVP; higher water contact angle; smoother release approaching zero-order	Useful when hydration and barrier functions need to coexist in one dosage form	[97]
KGM/SL/ε-PL	Functional ternary blending	Hydrogen bonding plus sulfonate/phenolic/electrostatic interactions reinforce the film	SL content; ε-PL loading; KGM concentration	Stronger film; lower WVP; antimicrobial activity reported	May support multifunctional protective or topical matrices, although direct transdermal benefit still requires testing	[98]
OKGM/CS	Oxidation + Schiff-base crosslinking	Aldehyde bearing OKGM reacts with chitosan amines to form dynamic imine bonds	Degree of oxidation; CS:OKGM ratio; pH 5–6	Higher G′ and modulus; lower pore size; self healing; lower WVP; reduced burst tendency	Particularly relevant for cohesive hydrogel reservoirs or adaptive soft matrices	[99]
KGM/CUD	Freeze–thaw structuring	Ice crystal formation densifies the network and increases structural packing during cycling	−20 °C; 12–48 h; cycle number	Higher G′ (around 9.9 kPa); greater hardness; lower water holding capacity	Useful for physically reinforcing soft KGM matrices without chemical crosslinkers	[100]
KGM/PVA nanofiber	Electrospinning	Nanofiber architecture increases surface area and reorganizes diffusion pathways	KGM:PVA ratio; voltage; collector distance	Higher tensile strength and elongation; more controlled release behavior	Suitable for thin, flexible, fibrous matrices with more structured transport behavior	[101]

Figure 5.

A decision tree framework for selecting the most appropriate modification route according to the dominant limitation of the native KGM matrix (Created in BioRender. Sriwidodo S (2026) https://BioRender.com/jyrrlrr).

Taken together, the studies summarized in Table 2 do not identify a single modification route as consistency superior. Partial deacetylation can improve chain association and gel strength, although the response is not linear. At higher degrees of deacetylation, hydration decreases and mechanical performance may decline after an optimum is reached.54,96 Oxidation and freeze thaw treatment can produce denser or more cohesive networks, but reduced water mobility may also limit swelling and solute diffusion.99,100 Bilayer construction and nanofiber formation offer a different approach by assigning separate functions to distinct layers or fibers rather than relying only on stronger crosslinking.101,102 Differences among studies are likely related to KGM source, molecular weight, degree of acetylation, polymer ratio, processing history, and test conditions. Therefore, higher strength or slower release should be interpreted as formulation specific outcomes and not as direct evidence of better transdermal performance.

Glucomannan Based Formulation Platforms for Transdermal Delivery

Recent studies place KGM into five main formulation platforms relevant to skin applied delivery, namely film-based matrices, hydrogel reservoirs, injectable hydrogels, nanofibrous or carrier assisted systems, and layered or hybrid architectures45,46,103–105 (Figure 6).

Figure 6.

Classification of KGM based formulation platforms relevant to transdermal drug delivery (Created in BioRender. Sriwidodo, S (2026) https://BioRender.com/4qvao1k).

This classification is useful because it shows that the role of KGM is primarily structural and platform dependent, with performance shaped by formulation architecture rather than by the polymer alone.45,102,104

Film Based Matrices

Film based matrices represent the most direct route for adapting KGM to patch oriented delivery because they place the polymer in a continuous thin layer that can support skin contact, hydration, and drug release control when reinforced by a second polymer phase.102,106

In resveratrol loaded chitosan/KGM films, release reached about 84% in one formulation and about 56% in another, while the BR10 system showed swelling of about 581% at pH 7.4, indicating that KGM rich films can sustain high water uptake together with substantial drug liberation.46

Electrospun KGM/PVA nanofibers provide more skin relevant evidence for this platform. Yang et al found that adding KGM increased fibrinogen adsorption and supported skin repair in cell and animal models.101 These findings suggest that KGM can contribute to a biologically interactive fibrous surface. However, the study focused on wound healing and did not measure drug transport across intact skin. It therefore supports skin compatibility and material design rather than transdermal efficacy.101,103

Bilayer chitosan/KGM films showed lower swelling and water vapor permeability than the corresponding single polymer films at selected composition.102 However, layering did not improve every property. Mechanical performance remained dependent on composition, while indicate that layered construction can improve moisture control, but strength, flexibility, and storage stability still require separate optimization.

Hydrogel Reservoirs

Hydrogel reservoirs form the second major platform because they make fuller use of the water binding capacity of KGM within a three dimensional hydrated matrix intended for soft contact and sustained release behavior.45,107

In KGM/oxidized hyaluronic acid hydrogels, increasing the OHA fraction increased swelling capacity and rheological strength, and the cumulative release rate of EGCG also increased with increasing OHA content, showing that KGM can function as part of a reservoir type network whose transport behavior is regulated by composition.45

In carboxymethyl chitosan/oxidized KGM hydrogels loaded with honokiol micelles, gel time remained below 10 min, water content remained above 92%, and hemolysis stayed below 5%, indicating a hydrated reservoir platform with favorable injectability, self healing, and biological compatibility.108

In oxidized glucomannan/chitosan hydrogels crosslinked with Mg²⁺, bacteriostatic rates exceeded 95% against both S. aureus and P. aeruginosa, showing that KGM based reservoir systems can also be combined with additional antimicrobial and anti inflammatory functions when required by the application context.108

Although these hydrogels provide useful evidence of water retention, network recovery, hemocompatibility, and local wound repair, their relevance to transdermal delivery remains indirect.107,108 The reported endpoints mainly concern antimicrobial activity and tissue healing rather than drug flux, skin deposition, or systemic exposure. These systems should therefore be considered evidence of skin contact functionality and short term biological performance, not confirmation of transdermal delivery.

Injectable Hydrogels

Injectable hydrogels represent a more dynamic extension of the reservoir platform because they are designed to undergo in situ gelation, recover after deformation, and respond to environmental triggers such as pH.105,109

In the pH-responsive chitosan/KGM system reported by Lin et al, incorporation of poly(aspartic hydrazide) improved mechanical properties and pH sensitivity, and bovine serum albumin release followed Fickian diffusion under different pH conditions, indicating that KGM can support adaptive injectable depots rather than only static hydrated matrices.105

In a later oxidized KGM/chitosan adhesive hydrogel, gelation occurred in about 30s, tissue adhesion reached 28.5 kPa, blood loss was reduced about threefold, coagulation time was shortened by about two-thirds, and wound closure reached 94% within 14 days, demonstrating that KGM can be incorporated into fast forming and highly conformable injectable platforms with strong interfacial performance.109

These studies show that KGM can support rapidly forming, adhesive, and recoverable soft depots.105,109 However, injection bypasses the stratum corneum, while wound closure does not demonstrate drug transport across intact skin. Injectable KGM hydrogels should therefore be presented as related skin delivery platforms that inform matrix design, rather than as direct evidence for conventional TDDS.

Nanofibrous and Carrier Assisted Platforms

Nanofibrous and carrier assisted systems extend the role of KGM beyond bulk films and hydrogels. KGM/PVA nanofibers increased fibrinogen adsorption and supported skin repair in cell and animal models, indicating that KGM can contribute to a biologically interactive fibrous surface.101 A separate KGM composite containing mesoporous polydopamine nanoparticles provided pH and near infrared responsive curcumin release.104 These studies show that formulation architecture can alter surface interactions and release control. However, neither system measured drug flux across intact skin, so their relevance to transdermal delivery remains preclinical and indirect.

Particulate and liposomal studies have also reported high drug loading and improved carrier stability after modification with carboxymethyl or oxidized KGM.110,111 KGM based gel spheres have shown sustained release under simulated intestinal conditions.17 Since these experiments used gastrointestinal models, they should be interpreted only as transferable evidence for carrier stabilization and release control, not as proof of skin delivery.

Multilayer Systems

Layered and hybrid systems distribute hydration, moisture control, and cargo handling across separate functional domains.

In bilayer chitosan/KGM films, selected compositions reduced swelling and water vapor permeability, although their mechanical and thermal responses remained dependent on the polymer ratio.102 By comparison, an oxidized KGM and carboxymethyl chitosan hydrogel containing mesoporous polydopamine nanoparticles provided pH and near infrared responsive curcumin release.104

These approaches address different formulation needs. Bilayer films offer a relatively direct means of controlling moisture transfer and matrix handling, whereas carrier containing hydrogels provide greater control over release triggers but require more complex preparation and characterization. Neither approach has yet demonstrated reliable drug transport across intact human skin. Platform selection should therefore be based on the intended drug, wear duration, target site, and required transport profile rather than on mechanical strength or cumulative release alone.

Drug Loading, Release Behavior, and Permeation Performance

KGM based systems have shown consistent capacity to incorporate active compounds into films, hydrogels, gel spheres, and carrier assisted matrices, but the available evidence is still stronger for loading and release control than for confirmed transdermal delivery.45,46,104,111

Drug incorporation in KGM systems follows two main routes. Direct matrix loading places the active compound within the continuous polymer network, as reported for EGCG and resveratrol.45,46

Carrier assisted loading first confines the drug within a particulate phase before the carrier is embedded in or coated with KGM.104,110,111 This approach may improve loading or protect unstable compounds, but it also introduces additional variables such as particle size, coating integrity, carrier distribution, and compatibility with the surrounding matrix.

Release profiles cannot be compared directly across these studies because the drugs, release media, matrix dimensions, and sampling conditions differ. Faster release may reflect greater swelling or weaker drug and polymer association, while slower release may result from a denser network density, carrier retention, or limited drug solubility.17,45,104 A high cumulative release value should therefore not be interpreted as better transdermal performance unless it is accompanied by skin flux, lag time, tissue deposition, and dose recovery.

What remains much less certain is how far these matrix level release results translate into true transdermal performance, because release from a KGM matrix does not necessarily indicate permeation across the skin.76,78

Among the available Benchmark studies, the BGP-15 patch provides a useful illustration. In porcine ear skin, 39.3% of the initial dose crossed the skin, while 9.2% remained in the tissue and the flux was 0.4647 mg/cm²·h.76 These finding show that release, tissue deposition, and passage across the skin are related but distinct outcomes.

An in vivo terahertz study further showed that occlusive PET backed patches increased stratum corneum hydration to about 60% after 24 h, compared with about 40% for woven patches.78 Because the study measured hydration rather than drug permeation, its result should not be interpreted as direct evidence of enhanced delivery. Instead, they demonstrate why hydration and transdermal transport should be evaluated as separate endpoints.

Cross study interpretation is further limited by differences in skin source, receptor medium, experimental duration, analytical stability, and the reporting of retained drug. The BGP-15 study quantified both permeation and tissue retention, whereas the apomorphine study emphasized validated analysis, drug stability, and deposition using a physiologically relevant porcine skin model. Adhesion testing of rotigotine patches also showed that moisture uptake can contribute to reduced interfacial performance. Future KGM studies should therefore assess release, skin transport, deposition, dose recovery, and adhesion within the same formulation rather than treating these outcomes as separate measures of performance.

Overall, current evidence supports KGM strongly as a loading supportive and release controlling matrix, especially in composite hydrogels, films, and carrier assisted systems, while direct evidence for robust skin permeation and systemic transdermal delivery remains limited.

Evaluation of Glucomannan Based Transdermal Systems

Evaluation of KGM based transdermal systems should follow a performance oriented framework, because acceptable swelling, mechanics, or release alone does not confirm transdermal suitability.30,45,46

In practice, KGM based matrices need to be assessed across a few linked domains, including uniformity, hydration related behavior, interfacial and mechanical performance, drug transport, safety and stability profile.76,78,112 Accordingly, Table 3 summarizes the main evaluation domains, key parameters, typical methods, and their practical relevance to KGM based transdermal systems.

Table 3.

Evaluation Framework for Glucomannan Based Transdermal Systems

Domain	Key Parameter	Common Methods	Practical Relevance for KGM Based TDDS	Ref.
Uniformity	Thickness	Micrometer; vernier caliper	Diffusion path; casting consistency	[113]
	Weight variation	Analytical balance	Batch consistency	[114]
	Drug content uniformity	Spectro UV-Vis; HPLC	Drug homogeneity	[115]
Moisture behavior	Moisture content	Moisture analyzer; oven drying	Softness/brittleness; storage stability	[116]
	Moisture uptake	RH storage; gravimetry	Humidity sensitivity; dimensional drift	[117]
	Swelling ratio	Gravimetric swelling test	Hydration expansion; release and integrity	[118]
	Water retention/ WHC	Retention test; gravimetry	Reservoir persistence; syneresis risk	[119]
Barier behavior	WVTR/ WVP	Cup method	Moisture exchange; occlusion behavior	[85]
Structure	Surface morphology	SEM	Cracks, pores, phase separation	[120]
	Internal microstructure (porosity)	SEM; image analysis	Diffusion pathway; densification	[121]
Interaction	Polymer-polymer/ drug polymer interaction	FTIR; ATR-FTIR	Confirms blending or crosslinking	[120]
Solid state	Thermal transitions	DSC; TGA	Matrix organization; storage effect	[122]
	Crystallinity/ amorphous change	XRD	Release and dissolution behavior	[123]
Rheology	Apparent viscosity	Rotational rheometer	Processability; casting/ gelling window	[124]
	Shear thinning behavior	Flow sweep	Shear handling; coating/casting suitability	[125]
	Storage modulus (G′)	Oscillatory rheology	Elastic strength; gel coherence	[126]
	Loss modulus (G″)	Oscillatory rheology	Viscous behavior; gel classification	[127]
	Recovery / self healing	Step strain; cut and heal	Structural recovery after stress
Film mechanics	Tensile strength	Texture analyzer	Fracture resistance; handling	[4]
	Elongation at break	Texture analyzer	Flexibility; skin movement tolerance	[128]
	Young’s modulus	Texture analyzer	Stiffness; conformity	[128]
	Folding endurance	Folding test	Repeated bending resistance	[116]
Hydrogel mechanics	Compressive strength	Texture analyzer; compression	Collapse resistance	[129]
	Compressive modulus	Texture analyzer; compression	Structural persistence	[130]
	Hardness	Texture analyzer	Firmness; handling comparison	[71]
Interface	Contact angle	Goniometer	Wettability; surface interaction	[30]

Abbreviations: ATR-FTIR, attenuated total reflectance Fourier transform infrared spectroscopy; CKGM, carboxymethyl konjac glucomannan; CS, chitosan; CUD, curdlan; DA, degree of acetylation; DSC, differential scanning calorimetry; dKGM, deacetylated konjac glucomannan; EGCG, epigallocatechin gallate; FTIR, Fourier transform infrared spectroscopy; HEC, hydroxyethyl cellulose; HME, hot melt extrusion; HPLC, high performance liquid chromatography; KGM, konjac glucomannan; KOGM, konjac oligo-glucomannan; LPDP, Indonesian Endowment Fund for Education; OHA, oxidized hyaluronic acid; OKGM, oxidized konjac glucomannan; OVA, ovalbumin; PEC, polyelectrolyte complex; PET, polyethylene terephthalate; PPI, pea protein isolate; PLGA, poly(lactic-co-glycolic acid); PVA, polyvinyl alcohol; PVP, polyvinylpyrrolidone; RH, relative humidity; SEM, scanning electron microscopy; TDDS, transdermal drug delivery systems; TGA, thermogravimetric analysis; UV-Vis, ultraviolet visible spectroscopy; WHC, water holding capacity; WVP, water vapor permeability; WVTR, water vapor transmission rate; XG, xanthan gum; XRD, X-ray diffraction.

Future Perspectives

Although recent studies have shown that KGM can be engineered into films, hydrogels, bilayer systems, and carrier assisted matrices, the current evidence still supports it more strongly as a promising formulation material than as a fully validated transdermal platform.

Most published work remains centered on swelling control, matrix reinforcement, and in vitro release, whereas durable adhesion, ex vivo permeation, and long wear performance are still much less consistently demonstrated.46,76,112

Future progress should therefore move beyond matrix level optimization toward a more complete demonstration of skin interface behavior and true barrier transport performance.

One major priority is the development of platform specific design logic rather than treating KGM as a universally applicable excipient across all transdermal formats.102,103,105

Film based systems appear more practical when dimensional control and patch handling are the main targets, whereas hydrogel systems are better suited to hydrated reservoir concepts and soft interfacial contact.102,105

Hybrid architectures, including bilayer matrices, nanofibrous systems, and nanoparticle assisted hydrogels, are especially promising because they allow hydration, structural support, and release control to be distributed across different functional domains. Another important direction is the integration of KGM with more advanced skin interfacing technologies that can address the current gap between release and actual delivery.109,131

Microneedle enabled systems, adhesive self-healing hydrogels, and stimuli-responsive composites suggest that KGM may become more valuable when incorporated into multifunctional platforms rather than used as a stand alone matrix.104,109,131

The next stage should follow a staged evidence pathway. Candidate KGM systems should first be evaluated through release and ex vivo permeation studies using a defined skin source, controlled skin thickness and integrity, validated analytical methods, and complete dose recovery. Formulations that meet these criteria should then be assessed for adhesion during movement, repeated wear, skin irritation, sensitization, and pharmacokinetic performance. Existing KGM studies provide useful short term evidence from wound and tissue repair models, but they do not establish long term safety after repeated application to intact human skin.

Translation also depends on product focused material control. KGM source, purity, molecular weight, degree of acetylation, moisture content, residual processing reagents, and batch variability should be predefined and linked to product attributes such as swelling, mechanical behavior, adhesion, drug content, release, permeation, and storage stability. From a regulatory development perspective, this evidence is more informative than describing KGM as safe solely because it is naturally derived. Reproducible manufacturing, packaging, storage, and performance after scale up should therefore be evaluated using the final dosage form. Collectively, these priorities define the proposed translational pathway for KGM based TDDS, as summarized in Figure 7.

Figure 7.

Translational roadmap and future priorities for KGM based transdermal systems (Created in BioRender. Sriwidodo, S (2026) https://BioRender.com/cfyw8kb).

Conclusion

Konjac glucomannan has emerged as a promising gel-forming biopolymer for transdermal systems because it combines strong hydration capacity, matrix forming ability, and structural tunability. Current evidence shows that KGM is especially valuable in films, hydrogels, and hybrid platforms, where its performance can be improved through blending, crosslinking, deacetylation, and architectural design.

At present, the strongest support for KGM lies at the level of material and formulation performance rather than fully validated transdermal efficacy. Future studies should standardize molecular weight, degree of acetylation, purity, and batch variability, then relate these attributes to adhesion, drug release, skin permeation, and stability. Validation should extend beyond in vitro testing to robust ex vivo and in vivo studies, preferably using human relevant skin models, repeated wear testing, and long term safety assessment. Scalable manufacturing and regulatory considerations should also be addressed early in development. These steps will clarify whether KGM can be translated into reproducible, safe, and clinically meaningful transdermal products.

Disclosure

The author(s) report no conflicts of interest in this work.