title: Brain delivery of transferrin coupled indinavir submicron lipid emulsions--pharmacokinetics and tissue distribution.
abstract: Indinavir, an antiretroviral protease inhibitor used in treatment of HIV infection has limited penetration into brain due to efflux of P-glycoprotein. The aim of this work was to develop transferrin coupled submicron lipid emulsions (SLEs) containing indinavir for delivery to brain. Stearylamine containing SLEs were prepared, characterized, tested for stability and optimized formulation (SLE-4) was developed. Transferrin was coupled to get SLE-6 by water soluble EDC method and purified by gel filtration. The coupled transferrin was quantified by modified Bradford dye assay method. The fluorescent dye (DiD oil) incorporated SLEs were used to check the brain specific delivery of SLEs. The in vivo pharmacokinetic and tissue distribution were conducted in mice. During pharmacokinetic studies, there was no significant difference in the serum levels of indinavir from SLE-1, SLE-4 and SLE-6 formulations at all time points. In tissue distribution studies the therapeutic availability (TA) of indinavir in brain from SLE-6 was 4.69, 3.1 and 1.7 times higher than drug solution, SLE-1 and SLE-4 respectively whereas, the TA of indinavir from SLE-4 was 2.76 and 1.82 times the drug solution and SLE-1. The brain to serum ratios with SLE-6 were above one indicates the brain specific delivery. The brain delivery of indinavir was improved with transferrin ligand attachment to SLEs by receptor mediated transcytosis.
authors.affiliation: Nanotechnology Laboratory, Department of Pharmaceutics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh, 506009, India.
authors.forename: Kandadi
authors.initials: K
authors.lastname: Prabhakar
authors.forename: Syed Muzammil
authors.initials: SM
authors.lastname: Afzal
authors.forename: Putcha Uday
authors.initials: PU
authors.lastname: Kumar
authors.forename: Ajumeera
authors.initials: A
authors.lastname: Rajanna
authors.forename: Veerabrahma
authors.initials: V
authors.lastname: Kishan
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002850:Chromatography, Gel; D004337:Drug Carriers / Q000378:metabolism / Q000493:pharmacokinetics*; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes / Q000032:analysis; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019469:Indinavir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008867:Microtomy; D010316:Particle Size; D011990:Receptors, Transferrin / Q000378:metabolism; D014018:Tissue Distribution; D014168:Transferrin / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D000588:Amines; D004337:Drug Carriers; D004655:Emulsions; D005456:Fluorescent Dyes; D017320:HIV Protease Inhibitors; D008055:Lipids; D011990:Receptors, Transferrin; D014168:Transferrin; D019469:Indinavir; C009317:stearylamine