Abstract
The least efficacy of most of the active pharmaceutical ingredients in the brain is attributed to the blood–brain barrier (BBB), which represents insurmountable obstacle for the effective management of majority of CNS disorders. The present research was planned with the objective to design novel poly (d, l) lactide (PLA) nanoparticles coupled with natural tripeptide i.e. glutathione to enhance drug delivery to brain. To evaluate the brain targeting efficiency of the glutathione conjugated nanoparticles, fluorescein sodium was explored as a model compound due to its polar nature and least possibility to cross BBB. The entrapment efficiency of fluorescein sodium was improved by screening several formulation variables like drug: polymer ratio, solvent selection, electrolyte addition and pH alteration. Scanning Electron Micrograph (SEM) and dynamic light scattering results of optimized formulation showed that prepared nanoparticles have a round and regular shape with a mean diameter of 257.8 ± 3.78 nm with narrow size distribution. Biodistribution pattern and brain targeting potential of optimized glutathione conjugated PLA nanocarriers was determined using wistar rat as an animal model in comparison to non-conjugated PLA nanoparticles and fluorescein sodium solution. The results showed significant increase in fluorescein sodium uptake in brain with glutathione conjugated PLA nanoparticles as compared to fluorescein sodium solution. The present investigations demonstrated that glutathione can serve as a potential ligand for brain drug delivery, which was observed with glutathione coupled PLA nanoparticles resulting into enhanced delivery of drug to nearly 5 folds in the brain.
Keywords: Blood brain barrier, glutathione, PLA nanoparticles, biodistribution
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