Comparative Stability of Synthetic and Natural Polymeric Micelles in Physiological Environments: Implications for Drug Delivery

Polymeric micelles are widely studied as nanocarriers for hydrophobic drugs, yet their structural stability under physiological conditions remains a major limitation. This review provides a comparative evaluation of synthetic and natural polymeric micelles with a focus on their stability under dilution and in protein-rich environments. The discussion integrates thermodynamic and kinetic factors governing micelle integrity and examines how molecular composition, hydrophobic segment length, and core–shell modifications influence disintegration behavior. While synthetic micelles commonly collapse below their critical micelle concentration during intravenous administration, natural polymeric micelles, such as those derived from chitosan, alginate, or heparin, exhibit improved resistance to dilution but remain vulnerable to protein-induced destabilization. Strategies such as core or shell cross-linking, surface functionalization, and natural polymer coatings are reviewed as promising approaches to enhance circulation stability and controlled drug release. The work provides a framework for designing micellar systems with balanced biocompatibility, biodegradability, and robustness suitable for clinical drug-delivery applications.