title: In situ hybrid nano drug delivery system (IHN-DDS) of antiretroviral drug for simultaneous targeting to multiple viral reservoirs: An in vivo proof of concept.
abstract: We report In situ hybrid nano drug delivery system (IHN-DDS) of nevirapine (NVP) for simultaneous targeting to multiple viral reservoirs. The IHN-DDS system was comprised of a preconcentrate containing NVP, lipid, and a surfactant which when diluted with water resulted in the formation of nanoparticles of size range varied from 70 to 1100nm. Transmission electron microscopy and small angle neutron scattering studies of pellet and supernatant obtained after centrifugation of the IHN-DDS revealed spherical shaped nanoparticles and assembled structures, respectively. Uniform distribution of the NVP in lipid nanoparticles was confirmed by fourier transform infrared spectroscopy. Biodistribution studies in rats showed significant enhancement of NVP concentration of about 6.1, 5.8 and 3.7 fold in the liver, spleen, and brain, respectively after intravenous administration of IHN-DDS systems compared to plain NVP solution. In conclusion, IHN-DDS systems could be a promising approach for simultaneous multisite targeting and could provide therapeutic benefits in complete eradication of HIV infections.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India; Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani Campus, Pilani 333031, Rajasthan, India.
authors.forename: Anil B
authors.initials: AB
authors.lastname: Jindal
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India.
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Bachhav
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India. Electronic address: pvdevarajan@gmail.com.
authors.forename: Padma V
authors.initials: PV
authors.lastname: Devarajan
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D053758:Nanoparticles / Q000008:administration & dosage; D019829:Nevirapine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine
keywords: Dimethylacetamide; Gelol; Lutrol F68; Poloxamer; Solid lipid nanoparticle