Surface modified biodegradable nanoparticles of Gabapentin. An approach to increase cell uptake

Abstract

Improving delivery to the regions of Central Nervous System has been a long-explored quest for scientists. Delivery through nanocarriers provide potential solution but it is also important to choose material which is biodegradable in nature. Further once administered inside body these nanocarriers get cleared from the system very fast leading to poor bioavailability. It is important to modify surfaces of nanoparticles with materials which can improve the residence time as well as cellular uptake of drugs at the site of action. In the present study poly (lactic-co-glycolic acid) (PLGA) was used as a biodegradable polymer wherein the surface of the nanoparticles was modified with a cationic polymer, chitosan. Chitosan has been widely used in drug delivery via nasal route as it imparts mucoadhesive property to the nanoparticle there by increasing its mean residence time. Gabapentin was encapsulated in PLGA nanoparticles as it belongs to BCS class III, with low solubility and low permeability thus make it a suitable choice for delivering via surface modified nanoparticles so as to increase bioavailability. Chitosan coated PLGA nanoparticle loaded with gabapentin were prepared by nanoprecipitation method. Surface modified nanoparticles were optimized and developed to obtain smaller particle size (180.7 nm), zetapotential (36.7 mV) and maximum entrapment efficiency (75.6%). Optimized chitosan coated PLGA nanoparticle was further evaluated for its surface morphology by FTIR & DSC. Spherical nature of the nanoparticles was evaluated by SEM & TEM. Biphasic release pattern was observed for surface modified nanoparticles with sustained release up to 72 h. Optimized formulation was evaluated for % cell viability in comparison with uncoated nanoparticles and drug solution alone via MTT assay on Neuro-2a cells. Nanoparticle localization in neuro-2a cells was assessed by Confocal Laser Microscopy when treated with Rhodamine123 labelled Chitosan coated PLGA nanoparticles. These findings suggest a significant enhanced uptake of surface modified PLGA nanoparticles was observed as compared to uncoated nanoparticles.