Thiolated Chitosan Masked Polymeric Microspheres with Incorporated Mesocellular Silica Foam (MCF) for Intranasal Delivery of Paliperidone

In this study, mesocellular silica foam (MCF) was used to encapsulate paliperidone, an antipsychotic drug used in patients suffering from bipolar disorder. MCF with the drug adsorbed was further encapsulated into poly(lactic acid) (PLA) and poly(lactide-co-glycolide) (PLGA) 75/25 w/w microspheres and these have been coated with thiolated chitosan. As found by TEM analysis, thiolated chitosan formed a thin layer on the polymeric microspheres’ surface and was used in order to enhance their mucoadhesiveness. These microspheres aimed at the intranasal delivery of paliperidone. The DSC and XRD studies showed that paliperidone was encapsulated in amorphous form inside the MCF silica and for this reason its dissolution profile was enhanced compared to the neat drug. In coated microspheres, thiolated chitosan reduced the initial burst effect of the paliperidone dissolution profile and in all cases sustained release formulations have been prepared. The release mechanism was also theoretically studied and three kinetic models were proposed and successfully fitted for a dissolution profile of prepared formulations to be found.