Design of a Reversible Cholinesterase Inhibitor Nanogel: Formulation and in vitro Evaluation

Memantine hydrochloride is a reversible cholinesterase inhibitor used to treat Alzheimer's disease. It is a low-moderate affinity, uncompetitive NMDA receptor antagonist with strong voltage dependency and rapid blocking/unblocking kinetics. The purpose of this study was to investigate the potential of a thermosensitive nanogel containing a mamentine-loaded nanoparticle. In situ gels are preferred because they limit unwanted exposure in blood and other healthy tissues, thereby eliminating hemolytic side effects and facilitating in-vivo administration. Ionic gelation method is used to prepare nanoparticles, and the dried nanoparticles are then incorporated with in situ gel. The in situ gel prepared by cold method using the solutions of Poloxamer-188 and Carbopol-934. Transmission electron microscopy revealed spherical particles with smooth surfaces, which agreed with SEM and Zetasizer data on particle size. The mucoadhesive strength of all formulations was varies from 2398±0.0004 to 4945±0.0002 dynes/cm2. In-vitro diffusion study of the in situ gel (N1-N8) was performed using modified Franz diffusion cell with dialysis membrane in phosphate buffer pH 6.5 for a period of 24 hours. The in vitro release data were fit into several kinetic models, including zero.order, first order, the Higuchi model, and the Korsmeyer-Peppas equation. Stability studies for optimized formulations were carried out at 4.0 ± 0.5°C and 37 ± 0.5ºC for a period of four weeks. The physical appearance, average particle size, and percentage drug content of the in situ nanogel N2 did not differ significantly. At the end of the storage period, no visible changes in the appearance of the gel formulation were observed.