Stavudine loaded gelatin liposomes for HIV therapy: Preparation, characterization and in vitro cytotoxic evaluation.
Despite continuous research and availability of 25 different active compounds for treating chronic HIV-1 infection, there is no absolute cure for this deadly disease. Primarily, the residual viremia remains hidden in latently infected reservoir sites and persistently release the viral RNA into the blood stream. The study proposes the dual utilization of the prepared stavudine-containing nanoformulations to control the residual viremia as well as target the reservoir sites. Gelatin nanoformulations containing very low dosage of stavudine were prepared through classical desolvation process and were later loaded in soya lecithin-liposomes. The nanoformulations were characterized through dynamic light scattering (DLS), Transmission electron microscopy (TEM), X-ray diffraction (XRD) and ATR-FTIR. All the formulations were in nano regime with high hemocompatibility and exhibited dose-dependent cytotoxicity towards Raw 264.7 macrophages. Among the various formulations, SG-3 (Stavudine-Gelatin Nanoformulation sample 3) and SG-LP-3 (Stavudine-Gelatin Nano-Liposome formulation sample 3) showed the best results in terms of yield, size, charge, encapsulation efficiency, hemocompatibility and % cell viability. For the first time, liposomal delivery of antiretroviral drugs using nanocarriers has been demonstrated using very low dosage (lower than the recommended WHO dosage) showing the prominent linear release of stavudine for up to 12h which would reduce the circulatory viremia as well as reach the sanctuary reservoir sites due to their nanosize. This method of liposomal delivery of antiretroviral drugs in very low concentrations using nanocarriers could provide a novel therapeutic alternative to target HIV reservoir sites.
Immunology and Molecular Medicine Laboratory, Department of Life Science, National Institute of Technology Rourkela 769008, Odisha, India.
Debasis
D
Nayak
Immunology and Molecular Medicine Laboratory, Department of Life Science, National Institute of Technology Rourkela 769008, Odisha, India.
Ankita
A
Boxi
Immunology and Molecular Medicine Laboratory, Department of Life Science, National Institute of Technology Rourkela 769008, Odisha, India.
Sarbani
S
Ashe
Immunology and Molecular Medicine Laboratory, Department of Life Science, National Institute of Technology Rourkela 769008, Odisha, India.
Neethi Chandra
NC
Thathapudi
Immunology and Molecular Medicine Laboratory, Department of Life Science, National Institute of Technology Rourkela 769008, Odisha, India. Electronic address: nayakb@nitrkl.ac.in.
Bismita
B
Nayak
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D020285:Cryoelectron Microscopy; D065546:Drug Liberation; D000067493:Dynamic Light Scattering; D005780:Gelatin / Q000737:chemistry*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008081:Liposomes; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D000067996:RAW 264.7 Cells; D017550:Spectroscopy, Fourier Transform Infrared; D018119:Stavudine / Q000494:pharmacology* / Q000627:therapeutic use*; D014961:X-Ray Diffraction
D019380:Anti-HIV Agents; D008081:Liposomes; D005780:Gelatin; D018119:Stavudine
Drug delivery; Gelatin; Liposomes; Macrophages; Nanoparticles; Stavudine