Targeted brain delivery of AZT via transferrin anchored pegylated albumin nanoparticles

Hydrophilic drugs/peptides have poor cross Blood-brain permeability. Various drug delivery systems with diverse surfacial characteristics have been reported for effective translocation of drugs across Blood-brain barrier. In present investigation, the potential of engineered albumin nanoparticles was evaluated for brain specific delivery after intravenous administration. Long circulatory PEGylated albumin nanoparticles encapsulating water-soluble antiviral drug azidothymidine (AZT) were prepared by ultra-emulsification method using chemical cross-linking by glutaraldehyde. Surface of the PEGylated nanoparticles was modified by anchoring transferrin as a ligand for brain targeting. Nanoparticles were characterized for their size, polydispersity, surfacial charge, drug loading and in vitro drug release. Fluorescence studies revealed the enhanced uptake of transferrin-anchored nanoparticles in the brain tissues when compared with unmodified nanoparticles. In vivo evaluation was carried out on albino rats to evaluate tissue distribution of engineered nanoparticles after intravenous administration. A significant (*P < 0.01) enhancement of brain localization of AZT was observed for transferrin anchored pegylated albumin nanopariticles (Tf-PEG-NPs). Hence, the specific role of transferrin ligand on nanoparticles for brain targeting was confirmed.