In vitro & in vivo evaluations of PLGA nanoparticle based combinatorial drug therapy for baclofen and lamotrigine for neuropathic pain management.

ABSTRACT

AIM: Baclofen and Lamotrigine via PLGA nanoparticles were developed for nose-to-brain delivery for the treatment of Neuropathic pain. METHODS: Nanoparticles were prepared using the modified nano-precipitation method. The prepared NPs were characterised and further in vitro and in vivo studies were performed. RESULTS: The Bcf-Ltg-PLGA-NPs were ∼177.7 nm with >75%(w/w) drugs encapsulated. In vitro dissolution studies suggested zero-order release profiles following the Korsmeyer-Peppas model. In vitro cytotoxicity and staining studies on mammalian cells showed dose dependant cytotoxicity where nanoparticles were significantly less toxic (>95% cell-viability). ELISA studies on RAW-macrophages showed Bcf-Ltg-PLGA-NPs as a potential pro-inflammatory-cytokines inhibitor. In vivo gamma-scintigraphy studies on rats showed intra-nasal administration of 99mTc-Bcf-Ltg-PLGA-NPs showed Cmax 3.6%/g at Tmax = 1.5h with DTE% as 191.23% and DTP% = 38.61% in brain. Pharmacodynamics evaluations on C57BL/6J mice showed a significant reduction in licks/bites during inflammation-induced phase II pain. CONCLUSION: The findings concluded that the combination of these drugs into a single nanoparticle-based formulation has potential for pain management.

Baclofen and Lamotrigine loaded PLGA nanoparticles were prepared with a size of 177.7nm, PDI 0.057 and Zeta Potential −15.8 mVIn vitro cell lines based studies showed dose dependant cytotoxicity and Bcf-Ltg-PLGA-NPs were found to be pro-inflammatory cytokines inhibitorsIn vivo Pharmacokinetic studies showed Cmax 3.6%/g at Tmax = 1.5 h with Drug Targeting Efficiency 191.23% and Drug Target Organ Transport 38.61% in the brain for prepared nanoparticlesIn vivo pharmacodynamics studies showed a significant reduction in licks/bites during inflammation-induced phase II pain.