In Vitro and In Silico Analyses of Nicotine Release from a Gelisphere-Loaded Compressed Polymeric Matrix for Potential Parkinson’s Disease Interventions

Abstract

This study aimed to develop a prolonged-release device for the potential site-specific delivery of a neuroprotective agent (nicotine). The device was formulated as a novel reinforced crosslinked composite polymeric system with the potential for intrastriatal implantation in Parkinson’s disease interventions. Polymers with biocompatible and bioerodible characteristics were selected to incorporate nicotine within electrolyte-crosslinked alginate-hydroxyethylcellulose gelispheres compressed within a release rate-modulating external polymeric matrix, comprising either hydroxypropylmethylcellulose (HPMC), polyethylene oxide (PEO), or poly(lactic-co-glycolic) acid (PLGA) to prolong nicotine release. The degradation and erosion studies showed that the produced device had desirable robustness with the essential attributes for entrapping drug molecules and retarding their release. Zero-order drug release was observed over 50 days from the device comprising PLGA as the external matrix. Furthermore, the alginate-nicotine interaction, the effects of crosslinking on the alginate-hydroxyethycellulose (HEC) blend, and the effects of blending PLGA, HPMC, and PEO on device performance were mechanistically elucidated using molecular modelling simulations of the 3D structure of the respective molecular complexes to predict the molecular interactions and possible geometrical orientation of the polymer morphologies affecting the geometrical preferences. The compressed polymeric matrices successfully retarded the release of nicotine over several days. PLGA matrices offered minimal rates of matrix degradation and successfully retarded nicotine release, leading to the achieved zero-order release for 50 days following exposure to simulated cerebrospinal fluid (CSF).

In Vitro Performance Testing of Nanoparticulate Drug Products for Parenteral Administration

“…For parenteral nanosuspensions, selection of the release medium usually starts with artificial human blood plasma (47). However, artificial synovial fluid and simulated CSF have also been employed (47,48). For robust testing, due to the complex nature of the medium, the composition should be simplified while keeping the physiological parameters constant, such as pH 7.4 and osmotic pressure 285 mOsm/kg for blood plasma (49).…”

Pharmaceutical Particulates and Membranes for the Delivery of Drugs and Bioactive Molecules

“…To begin with, we collaborated with other experts in the field of pharmaceutical particulates and membranes to review the current state of inorganic nanoparticulates and nanomembranes based on their design, and the key factors for adjusting their morphology and size for their possible medical applications, especially as drug carrier materials (Mabrouk et al [1]). A very good example of these points can be seen in the paper by Kumar et al [2] who have developed a prolonged release device for site-specific delivery of a neuroprotective agent (nicotine). The device has been formulated as a novel reinforced crosslinked composite polymeric system with the potential for intrastriatal implantation for Parkinson's disease interventions.…”