Targeting of AIDS related encephalopathy using phenylalanine anchored lipidic nanocarrier

- To facilitate brain delivery of anti-HIV agents across the blood brain barrier (BBB) is an utmost qualification to treat acquired immunodeficiency syndrome (AIDS) related encephalopathy. This debut study explored facilitated transport of efavirenz (EFV, a non-nucleoside reverse transcriptase inhibitor) across BBB using phenylalanine anchored solid lipid nanoparticles (PA-SLN). Here, PA acted as a ligand which facilitated carrier mediated transport (CMT) via l-amino acid transporter i.e. LAT1 to traverse BBB.
- PA was coupled to SLN via amide linkage using carbodiimide chemistry resulting in nanometric PA-SLN (around 150 nm). Desired controlled drug release pattern was observed in vitro for more than 24 h. Pharmacokinetic study showed enhanced brain localization of PA-SLN after PA coupling. Ability to cross BBB was significantly higher for PA-SLN in transcytosis studies. Fluorescence imaging confirmed selective brain accumulation of PA-SLN.
- In whole, PA-SLN improved the EFV bioavailability and maintained therapeutic levels in the brain for an extended period of time that resulted in significant eradication of the viral load therein. Such nutrient tailored drug targeting could be promising brain delivery approach.