Chitosan-g-oligo(epsilon-caprolactone) polymeric micelles: Microwave-assisted synthesis and physicochemical and cytocompatibility characterization.

GLISONI R.J.; QUINTANA S.; MOLINA SOLER M.A.; CALDERÓN M.; MOGLIONI A.G.; SOSNIK A

Journal of Materials Chemistry B

ROYAL SOC CHEMISTRY

Año: 2015 vol. 3 p. 4853 - 4864

2050-7518

Aiming to produce mucoadhesive polymeric micelles for drug administration by mucosal routes, chitosan-g-oligo(epsilon-caprolactone) copolymers were synthesized by a microwave-assisted ring-opening polymerization of epsilon-caprolactone using chitosan as macroinitiator and methanesulfonic acid as solvent, catalyst and protecting group of the amine moieties. The reaction was conducted under very mild conditions and completed within 10 min with a monomer conversion above 90%. The grafting of oligo(epsilon-caprolactone) blocks to the free hydroxyl groups of chitosan was confirmed by ATR/FT-IR, 1H- and 13C-NMR, WAXD and thermal analysis (TGA/DSC). The molecular weight of the synthetic hybrid copolymers was determined by GPC and MALDI-ToF mass spectrometry. Polymeric micelles obtained by the solvent diffusion/evaporation method showed spherical shape (TEM and AFM), sizes between 111-154 nm and highly positive zeta-potential (>+50 mV) (DLS). In addition, they displayed good cell compatibility in the human lung adenocarcinoma epithelial line A549 and were readily up-taken by the cervical cancer cell line HeLa. Results of the encapsulation of the antituberculosis drug rifampicin showed better performance than other nanocarriers previously investigated (e.g., cyclodextrins). Moreover, the micelles conserved the mucoadhesiveness displayed by pristine chitosan and, in addition, are expected to transiently open tight cell junctions and lead to more prolonged residence times in mucosal tissues and greater drug bioavailability.