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Layer-by-Layer Assembled Nanostructured Lipid Carriers for CD-44 Receptor–Based Targeting in HIV-Infected Macrophages for Efficient HIV-1 Inhibition

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Abstract

Macrophages act as a cellular reservoir in HIV infection. Elimination of HIV from macrophages has been an unfulfilled dream due to the failure of drugs to reach them. To address this, we developed CD44 receptor–targeted, novel hyaluronic acid (HA)-coated nanostructured lipid carriers (NLCs) of efavirenz via washless layer-by-layer (LbL) assembly of HA and polyallylamine hydrochloride (PAH). NLCs were subjected to TEM analysis, size and zeta potential, in vitro release and encapsulation efficiency studies. The uptake of NLCs in THP-1 cells was studied using fluorescence microscopy and flow cytometry. The anti-HIV efficacy was evaluated using p24 antigen inhibition assay. NLCs were found to be spherical in shape with anionic zeta potential (−23.66 ± 0.87 mV) and 241.83 ± 5.38 nm particle size. NLCs exhibited prolonged release of efavirenz during in vitro drug release studies. Flow cytometry revealed 1.73-fold higher uptake of HA-coated NLCs in THP-1 cells. Cytotoxicity studies showed no significant change in cell viability in presence of NLCs as compared with the control. HA-coated NLCs distributed throughout the cell including cytoplasm, plasma membrane and nucleus, as observed during fluorescence microscopy. HA-coated NLCs demonstrated consistent and significantly higher inhibition (81.26 ± 1.70%) of p24 antigen which was 2.08-fold higher than plain NLCs. The obtained results suggested preferential uptake of HA-coated NLCs via CD44-mediated uptake. The present finding demonstrates that HA-based CD44 receptor targeting in HIV infection is an attractive strategy for maximising the drug delivery to macrophages and achieve effective viral inhibition.

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Acknowledgements

The authors are thankful to All India Council for Technical Education (AICTE-NAFETIC) for providing research facilities. The authors are also thankful to Dr.R R Gangakhedkar, former Director-in-Charge, and Dr. Samiran Panda, Director, ICMR-NARI, for their support. The technical assistance for analysis of flow cytometry by Ms. Leila Abadi is also appreciated.

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  1. Centre for Novel Drug Delivery Systems, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga (E), Mumbai, 400 019, India

    Ketan Mahajan, Satish Rojekar & Pradeep Vavia

  2. Department of Virology, National AIDS Research Institute, Plot No 73, G-block, M I D C, Bhosari, Pune, Maharashtra, 411 026, India

    Dipen Desai & Smita Kulkarni

  3. Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, 411007, India

    Gandhali Bapat & Smita Zinjarde

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  1. Ketan Mahajan
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Mahajan, K., Rojekar, S., Desai, D. et al. Layer-by-Layer Assembled Nanostructured Lipid Carriers for CD-44 Receptor–Based Targeting in HIV-Infected Macrophages for Efficient HIV-1 Inhibition. AAPS PharmSciTech 22, 171 (2021). https://doi.org/10.1208/s12249-021-01981-4

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