title: Targeting of AIDS related encephalopathy using phenylalanine anchored lipidic nanocarrier.
abstract: Transport of the anti-HIV agents across the blood-brain barrier (BBB) is a prerequisite to treat acquired immunodeficiency syndrome (AIDS) related encephalopathy. In the present study, we explored facilitated transport of efavirenz (EFV, a non-nucleoside reverse transcriptase inhibitor) across BBB using phenylalanine anchored solid lipid nanoparticles (PA-SLN). PA (amino acid micro-nutrient) was used 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 and coupling was confirmed by comparative infrared spectroscopic analysis. SLNs (SLN and PA-SLN) were nanometric in size (around 150nm) and possessed good entrapment efficiency (around 70%). In vitro drug release revealed controlled release pattern for more than 24h. In vivo studies showed 2-3-folds and 7-8-folds accumulation of PA-SLN in brain as compared to SLN and EFV, respectively. Further, transcytosis studies confirmed capability of PA-SLN to cross BBB i.e. 10-fold higher transcytosis potential as compared to EFV. Fluorescence microscopic imaging reassured enhanced brain localization of PA-SLN. Thus, PA-SLN improved the EFV bioavailability and maintained therapeutic levels in the brain for an extended period of time that can result in significant eradication of the viral load therein. Such nutrient mediated drug targeting could bring forth advances in biocompatible and biodegradable drug delivery systems.
authors.affiliation: Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar 470 003, MP, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Vyas
authors.affiliation: Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar 470 003, MP, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Jain
authors.affiliation: Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar 470 003, MP, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Hurkat
authors.affiliation: Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar 470 003, MP, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
authors.affiliation: Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar 470 003, MP, India. Electronic address: drskjainin@yahoo.com.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Jain
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000480:Alkynes; D000818:Animals; D048588:Benzoxazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism; D001927:Brain Diseases / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D002478:Cells, Cultured; D003521:Cyclopropanes; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010649:Phenylalanine / Q000737:chemistry*; D017208:Rats, Wistar; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D004337:Drug Carriers; D008055:Lipids; D018894:Reverse Transcriptase Inhibitors; D010649:Phenylalanine; C098320:efavirenz
keywords: BBB; Efavirenz; HIV; HIV associated dementia; Phenylalanine; SLN