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Abstract
The application of nicotine in the research phase of Alzheimer's disease (AD) treatment has shown promise. The present study was aimed at understanding the incorporation of nicotine into poly-lactic acid (PLA) and poly(D,L-lactic-co-glycolic) acid (PLGA) microparticles which were then re-incorporated into a cross-linked zinc-alginate-pectinate polyspheric multi-particulate system to be employed as a possible brain implant for the treatment of AD. The Box–Behnken design was employed to prepare 15 PLA-PLGA formulations, which were tested for their drug incorporation efficiency and release potential and subsequently optimized using multiple regression and an artificial neural network generalized feed-forward model. Based on the rapid burst effect from the microparticles, further incorporation was conducted in a zinc-alginate-pectinate system using ionotropic gelation. Although double incorporation continued to provide a burst effect, this was followed by a lag period for 7 days and a second phase of drug release.