Dual Loaded Nanostructured Lipid Carrier of Nano-Selenium and Etravirine as a Potential Anti-HIV Therapy
There is a dire need for dual-long-acting therapy that could simultaneously target different stages of the HIV life cycle and providing a dual-prolonged strategy for improved anti-HIV therapy while reducing oxidative stress associated with the prolonged treatment. Thus, in the present work, nanostructured lipid carriers of Etravirine were developed and modified with nano-selenium. The dual-loaded nanocarrier system was fabricated using the double emulsion solvent evaporation method, further screened and optimized using the design of experiments methodology.
Highlights
TMC-Se-NLCs showed synergistic effect for improved anti-HIV therapy.
SeNPs showed a protective effect in combating oxidative stress and HIV infection.
TMC-Se-NLCs showed higher intracellular uptake compared to the TMC solution.
Improved biodistribution of a drug in remote HIV reservoir sites of rats.
The spherical core-shell type of a system was confirmed with an electron microscope and small-angle neutron scattering, while XPS confirmed the presence of selenium at the core-shell of the nanocarrier. In vitro assessment against HIV1 (R5 and X4 strains) infected TZM-bl cells exhibited higher efficacy for the dual-loaded nanocarrier system than the plain drug, which could be attributed to the synergistic effect of the nano-selenium. Confocal microscopy and flow cytometry results exhibited enhanced uptake in TZM-bl cells compared to plain drug. A significant increase of GSH, SOD, CAT was observed in animals administered with the dual-loaded nanocarrier system containing nano-selenium, suggesting the protective potential of the lipidic nanoparticle containing the nano-selenium.
Improvement in the in vivo pharmacokinetic parameters was also observed, along with a higher accumulation of the dual-loaded nanocarrier in remote HIV reservoir organs like the brain, ovary, and lymph node. The results suggest the potential of a dual-loaded formulation for synergistically targeting the HIV1 infection while simultaneously improving the intracellular anti-oxidant balance for improving a prolonged anti-HIV therapy.
Article information: Satish Rojekar, Rohan Pai, Leila Fotooh Abadi, Ketan Mahajan, Mahendrakumar Prajapati, Smita Kulkarn, Pradeep Vavia, Dual Loaded Nanostructured Lipid Carrier of Nano-Selenium and Etravirine as a Potential Anti-HIV Therapy, International Journal of Pharmaceutics, 2021. https://doi.org/10.1016/j.ijpharm.2021.120986.