Table 4.
Summary of curcumin-loaded formulation technique using various polymers as a drug delivery system.
| Types of Particles | Formulation Technique | Polymer(s) | Concentration of Polymer(s) | Target System | Findings | Reference |
|---|---|---|---|---|---|---|
| Nanoparticle | Solution-enhanced dispersion by supercritical CO2 | Silk fibroin powder | N/A | Intestine (Colon) | Permeability, retention effect, and intracellular uptake efficiency have shown to be improved in a time-dependent manner with this formulation, thus enhancing the inhibitory activity of curcumin on CRC (>98%). Moreover, it has been found that at a concentration of ~10 μg/mL, toxicity on healthy human colon mucosal epithelial cells is reduced, mainly owing to its sustained drug release mechanism. | [41] |
| Nanoparticle | Oil-in-water emulsion-solvent evaporation technique | PEGylated (polyethylene glycol)-PLGA | N/A | Intestine (Colorectal) | Controlled drug release and higher intracellular drug concentrations are observed with this formulation, leading to an improved anticancer action toward the colorectal cancer cells. | [45] |
| Microcapsule | Electrospray | PLA | 1–7% | Intestine | High encapsulation efficiency of more than 95% is achieved with this formulation, as well as the sustained drug release system for up to 200 h. Moreover, a minimal cytotoxic effect and excellent biocompatibility are observed with this formulation too. | [40] |
| Solid lipid microparticles incorporated in cold-set emulsion-filled gels | Xanthan gum and soy protein isolate | Xanthan gum (0.1% w/v) Soy protein isolate (15% w/v) |
Curcumin is successfully encapsulated in this formulation with enhanced stability. | [46] | ||
| Microparticles | Ionotropic gelation | Chitosan and sodium alginate | Chitosan (0.47 mg/mL) Sodium alginate (0.63 mg/mL) |
Topical | This formulation has enhanced curcumin’s wound-healing effect with an encapsulation efficiency of 75%. Moreover, the safety of curcumin has also been confirmed at a concentration of less than 25 µg/mL. Sustained drug release is achieved with this formulation as well, proving the potential use of this biodegradable formulation to deliver curcumin topically. | [47] |
| Nanoparticle | Freeze-drying method | Polyvinyl alcohol (PVA) | 0.1% | Intestine (Colon) | The encapsulation efficiency and aqueous solubility of curcumin are improved. | [48] |
| Nanoparticles | Emulsification and crosslinking process | Sodium alginate | 0.6 mg/mL | Prostate | The slow release of curcumin from the nanoparticle is demonstrated, as well as a higher uptake by the cell. Moreover, its cytotoxic action toward the prostate cancer cells is also observed, without the presence of hemodialysis, proving its safety to be administered intravenously. | [49] |
| Nanoparticles | Co-precipitation approach | Sodium alginate | 40% | GIT | The fabricated nanoparticles exhibited an excellent sustained drug release profile in a pH-sensitive manner, with a prolonged duration of action. Owing to its high entrapping efficiency and pH-sensitive drug release property, it has been deemed as one of the potential approaches for targeted drug delivery systems. | [38] |
| Nanoparticles | Oil-in-water emulsion–solvent evaporation technique and Freeze-drying | Ovalbumin and κ-carrageenan | 0.05% | GIT | An excellent encapsulation efficiency is observed with this formulation whilst the stability against heat and light has improved. Moreover, an increased antioxidation event is observed too. A gradual release of curcumin from the formulation is also demonstrated, hence improving its bioavailability as well as stability in an acidic environment. | [50] |
| Liposome | N/A | 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(PEG2000)] (DSPE-PEG2000) |
2 mM | Intestine (Colon) | A better inhibitory action toward the colon cancer cells is observed with this formulation. | [51] |
| Hydrogel (Microgels) | Cold gelation or GDL-induced gel formation? | Whey protein aggregates and k-carrageenan | Whey protein aggregates (12.6% w/w) k-carrageenan (0.1 and 0.55%, w/w) |
Intestine (Colon) | The high trapping efficiency of curcumin is demonstrated with this formulation. With this formulation, curcumin is also protected from degradation and release in the upper GIT, hence, it is deemed as a potential drug delivery system that is targeted to the colon. | [52] |
| Nanoparticle | Electrospray | Chitosan, zein, and piperine | Chitosan (2%) Zein (5%) Piperine (1.21 mg/mL) |
Neuroblastoma cells | High trapping efficiency of curcumin of 92% is observed with this formulation, as well as, a great cytotoxic action toward the neuroblastoma cells at a concentration of 10–25 µg/mL. | [42] |
| Micelle | Nanoprecipitation | Methoxy PEG-poly(caprolactone) | - | Intestine (Colon) | This formulation has achieved a synergistic effect on killing the colon cancer cells. | [53] |
| Liposome/Nanofiber mats | Ethanol injection method/ Electrospinning technique | Gelatin and zein | Gelatin (20% w/w) Zein solutions (20% w/w) |
- | Improved stability and a high encapsulation efficiency of approximately 90% of curcumin are achieved with this formulation. Moreover, a slow release of curcumin from the formulation is also observed. | [54] |
| Nanoparticles | Co-precipitation OR layer-by-layer coating | Sodium alginate and chitosan | Sodium alginate (20 mg/mL) Chitosan (10 mg/mL) |
Breast | Sustained drug release and improved cellular uptake efficiency, as well as superior cytotoxic action toward cancer cells, are achieved with this formulation; hence, this formulation is deemed one of the most promising approaches to delivering drugs for cancer treatment. | [55] |
| Liposome | W/O emulsion mediated film dispersion method | DSPE-PEG2000 | - | Intestine (Colon) | It has been shown that this formulation can improve the cellular uptake and lysosome escape of curcumin. This formulation led to better inhibition of cell proliferation than the free curcumin in colon cancer cells. | [56] |
| Microencapsulated matrix/ Nanofibrous scaffold | Freeze gelation | Chitosan and sodium alginate | - | Topical (Wound) | Great cytotoxic action toward cancer cells is achieved with this formulation. Moreover, the formulation is also found to be stable against enzymatic degradation. | [57] |
| Micelles | - | Sodium alginate | - | - | Controlled drug release is demonstrated with this formulation for up to 5 h, under physiological conditions. Its safety to be used in humans is also demonstrated by the absence of aggregation and cell hemolysis. Rapid cellular uptake is also observed. Hence, it is deemed a safe and efficient drug delivery system for curcumin. | [58] |
| Complex coacervates | Complex coacervation method | Gum arabic and whey protein nanofibrils | - | GIT | High encapsulation efficiency of up to 99% is observed with this formulation. Moreover, an excellent antioxidation activity and controlled drug release mechanism are also observed under simulated GIT conditions. | [39] |
| Complexes | Solvent-free pH shifting method | Whey protein isolate | 20 mg/mL | GIT | It significantly improved the aqueous solubility, chemical stability, and antioxidation effect of curcumin. A controlled drug release was also observed. | [59] |
| Nanoparticle | Ionic gelation technique | Chitosan and sodium alginate | Chitosan (0.05% w/v) Alginate (0.025% w/v) |
- | A drug loading efficiency of up to approximately 90% was achieved. The sustain-release of curcumin following the zero-order kinetics was also achieved with this formulation. | [60] |
| Nanoparticles | Ionotropic gelation technique | Sodium alginate | 1% | Intestine (Colon) | An improved trapping efficiency, up to 95%, was observed in this formulation. Moreover, it has been demonstrated that the dissolution of prepared nanoparticles is extremely low in simulated gastric and intestinal fluid, where most of the drug is released in simulated colonic fluid. Moreover, the oral bioavailability of curcumin is also found to be enhanced by 5-fold after the encapsulation. | [43] |
| Sponge (Wound dressing) | Freeze-drying | Ring-shaped β-cyclodextrin, chitosan, and sodium alginate | Chitosan (1%) Alginate (1%) |
Topical | The drug release, rate of degradation, and water uptake profiles of the formulation were found to be suitable as a wound-dressing formulation, where this cutaneous formulation facilitated the wound-healing process. | [61] |
| Nanoparticles/Wound dressing | Emulsification–diffusion method | Polycaprolactone and sodium alginate | Polycaprolactone (2% w/v) Sodium alginate (4% w/v) |
Topical | It has a good absorbency ability to remove the possible exudates, with high mechanical strength. Gradual release of curcumin is also achieved with delayed degradation. | [62] |
| Microparticle | Spray drying | Gum arabic | 1% w/v | The microcapsules prepared with gum arabic and sodium alginate have very rough surfaces, whilst microcapsules prepared with chitosan have a smoother surface. The release profile is similar among the three formulations, where the total release times are 4 h, 2 h, and 35 min, in microparticles prepared with gum arabic, sodium alginate, and chitosan, respectively. High trapping efficiency up to 93.8% to 97.6% is also achieved. | [63] | |
| Sodium alginate | ||||||
| Chitosan | ||||||
| Biopolymer composite film | Mechanical blending and casting method | Bacterial cellulose, alginate, and gelatin | - | Topical | The fabricated film showed the potent anticancer effect against the oral cancer cells, with mucoadhesion time at 0.5 to 6 h to porcine mucosa, under the artificial saliva condition. | [64] |
| Microfibers | Ionotropic gelation method | Sodium alginate and gelatin | Sodium alginate (10–100%) Gelatin (10–90%) |
Topical | Prolonged release of curcumin, up to 85% in 72 h, was achieved. It is deemed a potential drug delivery system for wound management, owing to its significant wound-healing profile. | [65] |
| Microspheres | - | Chitosan | - | GIT | A pH-sensitive swelling profile and controlled drug release mechanism are seen with the prepared microspheres. The formulation has lesser toxicity effects and its safety has been proved in the study after being incubated against the normal cell line. Hence, it is considered a potential approach for the controlled drug delivery system. | [66] |
| Microparticles | Polyelectrolyte complexation and ionic crosslinking | i-carrageenan, gellan and chitosan | - | Intestine (Colon) | High encapsulation efficiency of 85.75% to 97.25% was observed with this formulation. The potential use of this oral formulation as the controlled-release colon-targeted drug delivery was also demonstrated in this study, where curcumin within the microparticles was found to be able to overcome the gastric barrier without being degraded. | [67] |
| Nanosphere | Ionotropic gelification | Sodium alginate, chitosan, β-cyclodextrin, and PEG | - | Breast | High encapsulation efficiency and slow release of curcumin were observed with this formulation. Moreover, its absorption was also improved with this formulation, while the cell proliferation of the breast cancer cells was significantly reduced after the treatment. | [68] |
| Microparticles | Vacuum spray drying | Jelly fig extract and dicalcium phosphate hydroxide | Jelly fig extract (1.5–4.5% w/w) Dicalcium phosphate hydroxide (0.075% w/w) |
GIT | High encapsulation efficiency up to 91.56% is achieved with this formulation. Moreover, the formulation also exhibits an improved antioxidation stability profile and a cumulative drug release of approximately 95.34% in 1 d. | [69] |
| Microbeads | In situ ion-exchange followed by simple ionotropic gelation technique | Sodium alginate | - | Intestine | Extended drug release is seen with this formulation, showing that it is a potential approach to delivering curcumin. | [70] |
| Nanoparticles/ Scaffolds |
- | Collagen, alginate, and PEG6000 | Collagen (1%) Alginate (2%) PEG6000 (50%) |
Topical | Owing to its improved permeability, bioavailability, and aqueous solubility achieved with this formulation, it facilitates the wound-healing process. Moreover, a good curcumin encapsulation profile was also observed. | [71] |
| Hydrogel beads | Ionotropic gelation method | Sodium alginate | 2% | GIT | A controlled release of curcumin was achieved with this formulation under simulated GIT conditions. | [72] |
| Nanoparticle | Nanoprecipitation | poly(D,L-lactide) | 5 mg/mL | Intestine (Colon) | This formulation revealed an improved curcumin’s biodistribution and anticancer profiles against the human colon cancer model. | [73] |
| Nanoparticles | - | Alginate oligosaccharides | 1% w/v | Intestine (Colon) | Encapsulation efficiency was 91%. Controlled drug release was achieved with this formulation but was partially inhibited under neutral conditions. The absorption of the fabricated nanoparticles by colon cancer cells was better than the free curcumin, thus improving its tumor cell target efficiency. Findings suggested that this formulation might be a promising approach in the treatment of colon cancer. | [44] |
| Hydrogel | Ionic gelation technique | Alginate and chitosan | - | Lung and breast | It has been demonstrated that this formulation has a better anticancer profile. | [74] |
| Microsphere/Microbead | Emulsion-templated ionic gelation | Sodium alginate/Chitosan | Sodium alginate (3%) | Breast | A pH-sensitive drug delivery system has been achieved with this formulation. Moreover, its anticancer activity has improved too. | [75] |
| Polymer Encapsulated Liposomes | pH-driven method after extrusion of liposomes | PEG, Eudragit®S100 | - | Intestines | PEG reduced the bile effect on digestion, and Eudragit®S100 blocked the early release of the encapsulated drug in the mouth and stomach. | [76] |
| Composite film | Physical crosslinking | Poly(vinylalcohol)(PVA)/gelatin | - | Wounded skin | Rapid wound healing was observed, and histopathology showed ordered collagen deposition and angiogenesis with fibroblast formation and increased expression of proinflammatory cytokines | [77] |
| hydrogel | Thin film hydration for curcumin micelles, solvent casting method for the hydrogel formation | Pluronic F-68 for curcumin micelles, Chitosan and carboxymethyl cellulose for the hydrogel | - | Wounded skin | The hydrogel was biocompatible both using 3T3-L1 fibroblasts cell and in vivo, and improved wound healing observed by histopathology | [78] |