Baclofen-loaded PLGA nanoparticles for neuropathic pain management: In-vitro and In-vivo Evaluation.

In the present work, PLGA nanoparticles of baclofen (Bcf-PLGA-NPs) were developed and optimized using nanoprecipitation method. The average particle size of the Bcf-PLGA-NP was found to be 124.8 nm, polydispersity index of 0.225 and zeta potential was found to be in the range of -20.4 mV. In-Vitro dissolution studies showed that baclofen was released from PLGA NPs in a sustained fashion from 50 % release in 2.5 hrs to 80-85% in 24 hrs. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on Neuro-2a neuroblastoma cell line showed comparably low cytotoxicity of Bcf-PLGA-NPs as compared to aqueous solution of Baclofen at reported Cmax values of the drug 737.6 ng/ml. To explore the nose-to-brain pathway, in-vivo studies were carried out in Sprague-Dawley rats by radiolabelling of Baclofen with technetium-99m (99mTc). Gamma scintigraphy images of the rats administered via intranasal route showed the maximum uptake of radiolabelled NPs from nose to brain at 3 h as compared to the rats administered with NPs intravenously and orally. To assess the baclofen concentration in brain and blood, bio distribution studies were performed and following intranasal route the NPs were dispersed in brain (3.5%/g) and blood (3%/g) at 3 h and these observations were in agreement with the gamma scintigrams. Hence, from the results it was suggested that the developed PLGA NPs could serve as a potential carrier for the baclofen in the treatment of neuropathic pain.