Preparation and characterization of N-acetylchitosan, N-propionylchitosan and N-butyrylchitosan microspheres for controlled release of 6-mercaptourine

In this paper, biodegradable N-acylchitosan microspheres were prepared by a water-in-oil (w/o) interfacial N-acylation method for controlled release of 6-mercaptourine (6-MP). Acetic, propionic, and n-butyric anhydrides were used as reagents for the interfacial N-acylation reaction to prepare N-acetylchitosan, N-propionylchitosan and N-butyrylchitosan microspheres. The onset time for the gelation of N-acylchitosan microspheres increased with increasing the molecular weight of used anhydride. While, the particle sizes of N-acetylchitosan microspheres (> 50 mu m), N-propionylchitosan microspheres (20-50 mu m) and N-butyrylchitosan microspheres (similar to 5 mu m) decreased with the increase of substituted acyl chain length. The introduction of long acyl chains onto chitosan not only increased hydrophobicity, but also interfered crystallization of the polymer chains, leading to affecting the swelling and drug release properties of prepared N-acylchitosan microspheres. Drug release rates of the N-acylchitosan microspheres decreased in the sequence of N-propionylchitosan (t(50%) similar to 19 h) > N-butyrylchitosan (t(50%) similar to 36 h) > N-acetylchitosan (t(50%) > 100 h), and were fitted with a two-phase percolation model. The enhancement of drug release for N-propionylchitosan and N-butyrylchitosan microspheres under lysozyme degradation were less significant than their N-acetylchitosan counterpart. The results suggested that the N-acylchitosan microspheres excipient as interesting candidates for drug delivery application. (c) 2005 Published by Elsevier Ltd.