CONTROLLED INSULIN RELEASE FROM CHITOSAN MICROPARTICLES

This study deals with the production of chitosan microparticles contai ning insulin by interfacial crosslinkage of chitosan solubilized in th e aqueous phase of a water/oil dispersion in the presence of ascorbyl palmitate. The use of ascorbyl palmitate as interfacial crosslinker is based on its amphiphilic properties allowing its disposition at the w ater/oil interface of the preparative dispersion, thus permitting cova lent bond formation with the amino groups of chitosan when its oxidati on to dehydroascorbyl palmitate takes place during microparticle prepa ration. This preparation method produced microparticles characterized by high loading levels of insulin, completely releasing the drug in ab out 80 h at an almost constant release rate as determined by spectroph otometric and spectrofluorimetric methods. In contrast, the replacemen t of ascorbyl palmitate by dehydroascorbyl palmitate provided micropar ticles incompletely releasing the incorporated drug and characterized by a non-constant release rate over time due to the higher lipophilici ty of dehydroascorbyl palmitate which hinders its disposition at the w ater/oil interface and thus decreases the crosslinking efficiency and increases the lipophilicity of the microparticle surface. The efficien cy of the spectrofluorimetric and spectrophotometric methods used for determination of the stability and release of the insulin from the chi tosan microparticles is also discussed.