OBJECTIVE Asiatic acid, a well-known plant-based neuroprotective pentacyclic triterpenoid, has major limitation for its bioavailability in the brain. The objective of this study is to develop novel bovine serum albumin (BSA) nanoparticles coupled with glutathione (natural tripeptide) to enhance drug delivery to brain. METHODS Asiatic acid-loaded BSA nanoparticles were prepared by using modified desolvation technique. Conjugation of glutathione with asiatic acid-loaded BSA nanoparticle was done by carbodiimide reaction using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC). In-vivo biodistribution study of asiatic acid solution, and conjugated and unconjugated asiatic acid-loaded BSA nanoparticles, at the dose equivalent to 75 mg/kg was evaluated, through intravenous administration to Wistar rats. Asiatic acid has very weak chromophore so high-pressure liquid chromatography-based novel pre-derivatization method was developed using p-toluidine as a coupling agent to improve sensitivity. RESULTS The results showed 10-fold more bioavailability of asiatic acid in the brain after 5 h with glutathione-conjugated asiatic acid-loaded BSA nanoparticles as compared with asiatic acid solution with 627.21% drug targeting efficiency to the brain. CONCLUSIONS The present investigation demonstrated enhanced delivery of asiatic acid using glutathione and hence served as a potential ligand to improve brain targeting efficiency.