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

GLISONI, ROMINA J.; QUINTANA L, SILVINA S.; MOGLIONI, ALBERTINA G.; GLISONI, ROMINA J.; GARCIA-FERNANDEZ, MARIA J.; PINO, MARYLU; GUTKIND, GABRIEL; MOGLIONI, ALBERTINA G.; ALVAREZ-LORENZO, CARMEN; CONCHEIRO, ANGEL; SOSNIK, ALEJANDRO SOSNIK; MOLINA, MARIA; CALDERON, MARCELO

Journal of Materials Chemistry B: Materials for Biology and Medicine

Royal Society of Chemistry

Año: 2015 vol. 3 p. 4853 - 4864

With the aim to produce mucoadhesive polymeric micelles for drug administration by mucosal routes, chitosan-​g-​oligo(epsilon-​caprolactone) copolymers were synthesized by the microwave-​assisted ring-​opening polymn. of epsilon-​caprolactone using chitosan as the macroinitiator and methanesulfonic acid as the solvent, catalyst and protecting group of the amine moieties. The reaction was conducted under very mild conditions and was 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 anal. (TGA​/DSC)​. The mol. wt. of the synthetic hybrid copolymers was detd. by GPC and MALDI-​ToF mass spectrometry. Polymeric micelles obtained by the solvent diffusion​/evapn. method showed a spherical shape (TEM and AFM) with sizes between 111 and 154 nm and highly pos. zeta potential (>+50 mV) (DLS)​. In addn., 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 from the encapsulation of the antituberculosis drug, rifampicin, showed that the micelles had better performance than other nanocarriers previously investigated (e.g., cyclodextrins)​. Moreover, the micelles conserved the mucoadhesiveness displayed by pristine chitosan and are expected to transiently open tight cell junctions and lead to more prolonged residence times in mucosal tissues and greater drug bioavailability.