Mechanistic evaluation of alginate-HEC gelisphere compacts for controlled intrastriatal nicotine release in Parkinson's disease

Abstract

This study focused on elucidating a mechanistic understanding in support of the multiple mechanisms which govern the formation of crosslinked alginate-hydroxyethylcellulose (Alg-HEC) gelispheres intended for the controlled intrastriatal release of nicotine as a neuroprotectant in Parkinson's Disease. HEC was incorporated as a reinforcing "protective" colloidal polymer to induce interactions between the free carboxyl groups of alginate with hydroxylated HEC monomers. Gelispheres were compressed within an external poly(lactic-co-glycolic acid) (PLGA) matrix to further prolong the release of nicotine. Sol-gel interconversion mechanisms, matrix deformability moduli, matrix fracture energies and chemometric models of the associated energy paradigms were analyzed for their influence on the mechanism and extent of nicotine release. Textural profiling demonstrated higher fracture energies (7.94-26.69×10-4 J) and lower deformability moduli (12.24-58.36 N/mm) when gelispheres were cured in 2 MHCl as a postcuring step. Ba 2+ crosslinked gelispheres resulted in superiorly compact matrices with an increase in volume of 201-329% as compared to the Ca2+ and Zn2+ crosslinked matrices. The order of matrix compactness was as follows: Zn2+