CROSS-LINKED CHITOSAN MICROSPHERES AS CARRIERS FOR PROLONGED DELIVERYOF MACROMOLECULAR

Bovine serum albumin (BSA) and diphtheria toroid (DT) were loaded by p assive absorption from aqueous solutions into preformed glutaraldehyde cross-linked chitosan microspheres. In vitro release of BSA under sin k conditions at 37 degrees C showed that even though there was a large burst effect, there was a more or less steady increase with time ther eafter for several days. Coating the BSA-loaded particles with paraffi n oil or with a polymer, such as polylactic acid, modulated drug relea se. After the initial burst from PLA coated particles, the release rat e increased with time for nearly 2 months. Preliminary immunogenicity studies on Wistar rats using DT loaded chitosan spheres showed that th e antibody titres were fairly constant over a 5-month period, although very low compared to DT given on alum as control. Histological studie s of placebo microspheres intramuscularly injected into rats demonstra ted their tissue compatibility. Biodegradation was not complete in 6 m onths demonstrating the potential of cross-linked chitosan spheres as a long-acting drug delivery vehicle. The study demonstrated the possib ility of incorporating biological macromolecules which are very sensit ive to organic solvents, pH, temperature, ultrasound, etc. by a passiv e absorption technique to degradable biopolymer matrices thereby prese rving their biological integrity. It is also shown that drugs passivel y absorbed into such matrices by taking advantage of their swelling be haviour need not necessarily be released completely in the initial 'bu rst' and a sustained release may be possible for macromolecules thus i ncorporated.