Table 3.

An overview of the stability, longevity challenges, and prospective solutions related to various biomimetic delivery systems.

BDS	Stability and Longevity Challenges	Prospective Solutions
Liposomes	Sensitivity to oxidation and hydrolysis. Fusion/aggregation in serum. Rapid clearance from circulation.	Liposome coating (e.g., PEGylation). Incorporation of cholesterol. Antioxidant inclusion.
Protein-Based NPs
Albumin nanoparticles	Instability in harsh environments (e.g., acidic pH). Enzymatic degradation.	Cross-linking of albumin molecules. Encapsulation with protective polymers. Surface modifications.
Protein-based nanocages	Structural disintegration at non-optimal conditions. Immune recognition and clearance.	Chemical surface modifications. Incorporation of stability-enhancing ligands. Fusion with other stable proteins.
VLPs	Potential immunogenicity. Stability issues due to dynamic protein structures.	Genetic modifications. Encapsulation within protective matrices. Surface modifications to reduce immunogenicity.
NDs	Sensitivity to physiologic conditions, leading to structural alteration. Potential immune recognition.	Use of stable lipids. Protective protein inclusion. Surface modification.
Fibroin and Gelatin	Sensitivity to temperature and pH. Enzymatic degradation in vivo.	Chemical cross-linking. Incorporation into composite materials. Coating with protective polymers.
EVs	Susceptibility to clearance mechanisms. Sensitivity to physiologic conditions leading to vesicle disruption.	Surface modifications. PEGylation. Encapsulation within biomaterials. Cryopreservation techniques.
CMDNs	Potential immunogenicity. Sensitivity to in vivo degradation mechanisms.	Immune camouflage techniques. Genetic modifications for enhanced stability. Surface modifications.
Polysaccharides
Alginate	Rapid degradation in vivo. Instability in the presence of divalent cations.	Cross-linking with divalent cations. Incorporation into composite materials. Layer-by-layer assembly.
Chitosan	Solubility issues in neutral and basic pH. Rapid degradation in vivo.	Chemical modifications for solubility. Cross-linking. Layer-by-layer assembly.
Hyaluronic acid	Rapid enzymatic degradation in vivo. Instability under harsh conditions.	Derivatization and cross-linking. Hydrogel formulations. Composite materials incorporation.
Dextran	Sensitivity to oxidative conditions. Enzymatic degradation.	Cross-linking. Encapsulation within protective matrices. Blend with other stable polymers.