Novel Quaternized Chitosan and Polymeric Micelles With Cross-Linked Ionic Cores for Prolonged Release of Minocycline

Abstract

Novel multifunctional octadecyl quaternized carboxymethyl chitosans (OQCMCs) with varying degree of quaternary substitution (DS) and molecular mass were prepared and compared with quaternized chitosan. OQCMCs exhibited excellent solubility both in water and organic solvents. Nanoparticles of OQCMCs offered many advantages, such as easier fabrication and modulation of their size and degree of positive charge, and a lower cytotoxic effect compared with PEI (25 kDa). DNA can be successfully adsorbed on its surface. Electrostatic attraction of carboxymethyl and quaternary groups in OQCMCs was utilized as micellar template for the synthesis of cross-linked micelles. Formation and characteristics of OQCMC polymeric micelles were studied by fluorescence spectroscopy, tensiometry, SEM, TEM and particle size analysis. Self-assembled OQCMC micelles were evaluated as carrier of the lipophilic drug, minocycline hydrochloride (MH). MH was incorporated into cross-linked ionic cores of micelles with remarkably high efficiency (22.7%, w/w). MH-loaded OQCMC polymeric micelles exhibited a slow steady release profile over a 1-week period at 37°C. The OQCMC micelles are potentially useful for gene and lipophilic drug delivery applications.

Keywords:

• QUATERNIZED CHITOSAN
• POLYMERIC MICELLES
• GENE VECTOR
• LIPOPHILIC DRUG