One-step preparation of multifunctional chitosan microspheres by a simple sonochemical method

Chitosan is a biodegradable natural polymer with great potential for pharmaceutical applications due to its biocompatibility, high charge densi-ty, nontoxicity, and mucoadhesion properties. Processing techniques for the preparation of chitosan micro-spheres have been extensively devel-oped since the 1980s. The present paper describes for the first time a fast and one-step process for the prepara-tion of stable chitosan microspheres by a simple sonochemical method. The microspheres were characterized by their particle size, surface morphology, stability, and drug-entrapment efficiency. The average size of the micro-spheres was found to be around 1 urn with a narrow size distribution, which enabled them to be used for in vivo ap-plications. The encapsulation of differ-ent dyes into these microspheres was readily achieved with more than 75% efficacy by dissolving them into the or-ganic phase before sonication. The chi-tosan microspheres demonstrated ex-cellent stability toward acidic and basic conditions ranging from pH 4 to 9, thereby indicating their implementa-tion as possible therapeutic and diag-nostic agents. The stability of these mi-crospheres appears to be contributed from intermolecular imine cross-linking in addition to other noncovalent inter-actions. The ability of the surface-ex-posed amino groups of chitosan micro-spheres to undergo chemical conjuga-tion with potential drugs and/or target-ing vectors was determined by their reaction with fluorescein isothiocyanate (FITC) and fluorescamine followed by confocal microscopy.