pH-dependent systems for colon delivery of vancomycin

Site-specific controlled release systems offer many advantages over classical methods of drug delivery. These include localized delivery of the drug to a particular part of the body, assurance of drug stability, reduced need for follow up care and optimized drug absorption. In particular the release of orally administred peptidic drugs has attracted growing interest in recent years following the developmet of new delivery systems able to overcome problems due to the acidic environment and enzymatic degradation in the gastrointestinal tract [1]. Chitosan (CH) is a natural derivative of chitin produced by partial N-deacetylation under alkaline conditions. Because of its amino groups, it is a weak base and is insoluble in water and in organic solvents, however it is soluble in dilute aqueous acid solutions (pH < 6.5). Chitosan is a polycation and is able to form salts with a wide variety of acids. Moreover it has interesting biological properties, including biocompatibility and biodegradability and it has been used extensively to prepare hydrogels and microparticles [2]. The aim of this study was to describe a pH-dependent drug release system based on chitosan salts for vancomycin hydrochloride delivery. Chitosan succinate (CH-Suc), chitosan adipate (CH-Ad) and chitosan suberate (CH-Sub) were prepared at different crosslinking degrees by spray-drying and coated with stearic acid by the same technique. Vancomycin hydrochloride was used as a peptidic model drug whose controlled release should minimize its inactivation in the upper part of the gastrointestinal tract. This study characterized the systems in terms of morphology, size, swelling and mucoadhesive properties, drug loading (as assessed by means of an original capillary electrophoresis method) and in particular evaluated, in vitro, the influence of chitosan salts on the release behaviour of vancomycin hydrochloride from the uncoated and coated systems at pH 2.0, 5.5 and 7.6. Chitosan salts provided different swelling and release behaviour as a function of diacid chain length and crosslinking degree according to a different polymer ability to interact with water. Moreover chitosan salts showed different swelling and release behaviour as a function of enviromental pH according to the net charge balance inside the gel. The coating process was found to prevent vancomicyn release in acidic conditions allowing the complete release of the peptidic drug in the intestinal fluids. Chitosan salts coated with stearic acid could serve as potential candidates for antibiotic colon-specific delivery. References [1] G. Van den Mooter , Expert Opin. Drug Deliv. 3 (2006) 111. [2] T. Cerchiara, B. Luppi, F. Bigucci and V. Zecchi, J. Pharm. Pharmacol. 55 (2003) 1623.