Design Development and Evaluation of Paclitaxel Nanoparticles for Intra Nasal Drug Delivery

Abstract

Delivery of drugs to brain is most challenging in the neuropharmaceutical research. Brain newlineis surrounded by stringent anatomical barrier i.e. blood brain barrier (BBB), which newlineexpressed number of efflux transporters on its surface and limits the entry of variety of newlineneuropharmaceutical to the brain which make the management of CNS disorders newlinerefractory to the available therapy. Hence, in view of proposed challenges, present newlineinvestigation focused on the development of nanoparticulate carriers functionalized with newlinegutathione for delivering drug / marker compound to the brain through intra-nasal route. newlineIn present exploration fluorescein sodium and paclitaxel were explored as a model newlinecompounds because of their low permeability across the BBB and also found to be a newlinesubstrate for P-gp (P-glycoprotein) and multidrug resistance proteins which further newlinerestricts its entry to the brain. newlineIn present investigation, nanoparticles of poly lactide co-glycolide (PLGA, 50:50) and newlinehuman serum albumin (HSA) were developed using modified nanoprecipitation and newlinemodified desolvation technique. Further fluorescein sodium, and paclitaxel loaded newlinenanoparticles were prepared and optimized for drug entrapment, particle size and drug newlinerelease properties using Design of Experiments. Glutathione was appended on the surface newlineof drug loaded nanoparticles using carbodiimide chemistry. Glutathione conjugated and newlineun-conjugated nanoparticles were characterized for its size, drug entrapment, morphology, newlinedrug release profile and for in-vitro, ex-vivo and bio-distribution studies. newlineIn-vitro drug release studies were performed using dialysis bag technique. The drug newlinerelease from the nanoparticles exhibited Weibull pattern i.e. initial burst release followed newlineby slower release over extended period of time. Ex-vivo permeation studies were newlineconducted across sheep nasal mucosa using Franz diff