Mahajan, Ketan and Rojekar, Satish and Desai, Dipen and Kulkarni, Smita and Vavia, Pradeep (2020) Efavirenz Loaded Nanostructured Lipid Carriers for Efficient and Prolonged Viral Inhibition in HIV-Infected Macrophages. Pharmaceutical Sciences, 27 (3). pp. 418-432. ISSN 1735-403X
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Abstract
Background: The clinical outcome of anti-HIV therapy is poor due to the inherent fallouts ofanti-HIV therapy. It is further worsened due to the presence of viral reservoirs in immune cellslike the macrophages. An ideal anti-HIV therapy must reach, deliver the drug and exert itsaction inside macrophages. To address this, we developed novel cationic nanostructured lipidcarriers of efavirenz (cationic EFV-NLC).
Methods: The developed cationic EFV NLCs were evaluated for particle size, zeta potential,encapsulation efficiency, in-vitro drug release, DSC, XRD, TEM, cytotoxicity, cellular uptakestudies and anti-HIV efficacy in a monocyte-derived macrophage cell line (THP-1).
Results: Cationic EFV-NLCs showed high encapsulation efficiency (90.54 ± 1.7%), uniformparticle size distribution (PDI 0.3-0.5 range) and high colloidal stability with positive zetapotential (+23.86 ± 0.49 mV). DSC and XRD studies confirmed the encapsulation of EFVwithin NLCs. Cytotoxicity studies (MTT assay) revealed excellent cytocompatibility (CC5013.23 ± 0.54 μg/mL). Fluorescence microscopy confirmed the efficient uptake of cationic EFVNLCs,while flow cytometry revealed time and concentration dependant uptake within THP-1cells. Cationic EFV-NLCs showed higher retention and sustained release with 2.32-fold higherpercent inhibition of HIV-1 in infected macrophages as compared to EFV solution at equimolarconcentrations. Interestingly, they demonstrated 1.23-fold superior anti-HIV efficacy over EFVloadedNLCs at equimolar concentrations.
Conclusion: Cationic NLCs were capable of inhibiting the viral replication at higher limitsconsistently for 6 days suggesting successful prevention of HIV-1 replication in infectedmacrophages and thus can prove to be an attractive tool for promising anti-HIV therapy.
Item Type: | Article |
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Subjects: | Open Archive Press > Medical Science |
Depositing User: | Unnamed user with email support@openarchivepress.com |
Date Deposited: | 13 May 2023 05:39 |
Last Modified: | 21 Oct 2024 04:15 |
URI: | http://library.2pressrelease.co.in/id/eprint/1223 |