title: Stealth anti-CD4 conjugated immunoliposomes with dual antiretroviral drugs--modern Trojan horses to combat HIV.
abstract: Highly active antiretroviral therapy (HAART) is the currently employed therapeutic intervention against AIDS where a drug combination is used to reduce the viral load. The present work envisages the development of a stealth anti-CD4 conjugated immunoliposomes containing two anti-retroviral drugs (nevirapine and saquinavir) that can selectively home into HIV infected cells through the CD4 receptor. The nanocarrier was characterized using transmission electron microscopy, FTIR, differential scanning calorimetry, particle size and zeta potential. The cell uptake was also evaluated qualitatively using confocal microscopy and quantitatively by flow cytometry. The drug to lipid composition was optimized for maximum encapsulation of the two drugs. Both drugs were found to localize in different regions of the liposome. The release of the reverse transcriptase inhibitor was dominant during the early phases of the release while in the later phases, the protease inhibitor is the major constituent released. The drugs delivered via anti-CD4 conjugated immunoliposomes inhibited viral proliferation at a significantly lower concentration as compared to free drugs. In vitro studies of nevirapine to saquinavir combination at a ratio of 6.2:5 and a concentration as low as 5 ng/mL efficiently blocked viral proliferation suggesting that co-delivery of anti-retroviral drugs holds a greater promise for efficient management of HIV-1 infection.
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), SASTRA University, Thanjavur, India.
authors.forename: Lakshmi Narashimhan
authors.initials: LN
authors.lastname: Ramana
authors.affiliation: HIV-AIDS Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore, India.
authors.forename: Shilpee
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), SASTRA University, Thanjavur, India.
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Sethuraman
authors.affiliation: HIV-AIDS Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore, India.
authors.forename: Udaykumar
authors.initials: U
authors.lastname: Ranga
authors.affiliation: Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), SASTRA University, Thanjavur, India. Electronic address: umakrishnan@sastra.edu.
authors.forename: Uma Maheswari
authors.initials: UM
authors.lastname: Krishnan
mesh_terms: D019380:Anti-HIV Agents / Q000276:immunology* / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015704:CD4 Antigens / Q000276:immunology*; D004337:Drug Carriers / Q000737:chemistry; D057809:HEK293 Cells; D006678:HIV / Q000187:drug effects* / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008055:Lipids / Q000737:chemistry / Q000276:immunology; D008081:Liposomes / Q000276:immunology* / Q000494:pharmacology*; D053758:Nanoparticles / Q000737:chemistry; D019829:Nevirapine / Q000276:immunology / Q000494:pharmacology; D019258:Saquinavir / Q000276:immunology / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D015704:CD4 Antigens; D004337:Drug Carriers; D017320:HIV Protease Inhibitors; D008055:Lipids; D008081:Liposomes; D019829:Nevirapine; D019258:Saquinavir
keywords: Anti-CD4; Dual drug loaded anti-CD4 conjugated anti-CD4 conjugated immunoliposomes; HIV; Nevirapine; Saquinavir; Targeting; Viral load