Research Article

School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, PA 19140, USA

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Hui Yi Xue

School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, PA 19140, USA

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Ngoc T Tran

School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, PA 19140, USA

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Kamel Khalili

Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA

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Rafal Kaminski

Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA

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Ho Lun Wong

*Author for correspondence: Tel.: +1 215 707 8173;

E-mail Address: ho-lun.wong@temple.edu

School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, PA 19140, USA

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Published Online:10 Oct 2023https://doi.org/10.2217/nnm-2023-0120

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Abstract

Aim: To develop lipid nano-antiretrovirals (LNAs) for the treatment of HIV-infected macrophages. Materials & methods: LNAs were prepared with docosahexaenoic acid to facilitate brain penetration and surface-decorated with folate considering that infected macrophages often overexpress folate receptors. Results: Folate-decorated LNAs loading rilpivirine (RPV) were efficiently taken up by folate receptor-expressing cell types including activated macrophages. The intracellular C_max of the RPV-LNAs in activated macrophages was 2.54-fold and the area under the curve was 3.4-fold versus free RPV, translating to comparable or higher (p < 0.01; RPV ≤6.5 ng/ml) activities against HIV infectivity and superior protection (p < 0.05) against HIV cytotoxicity. LNAs were also effective in monocyte-derived macrophages. Conclusion: These findings demonstrate the potential of LNAs for the treatment of infected macrophages, which are key players in HIV reservoirs.

Plain language summary

HIV can infect and hide inside certain types of white blood cells that make up the immune system and help defend our body, such as macrophages. Because these infected cells tend to carry the virus to certain organs where antiviral drugs have a hard time reaching, the virus is able to avoid treatment from the drug. In this study, the authors developed very small devices known as nanocarriers to carry antiviral drugs. These nanocarriers were designed to seek out infected macrophages. The nanocarriers were successfully built with oils and lipids that are safe for patients and could easily deliver antiviral drugs to macrophages infected by HIV. Excellent anti-HIV effects were observed using these nanocarriers. In summary, the authors developed a promising device with the potential to fight HIV in a smart and safe manner.

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Papers of special note have been highlighted as: • of interest

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Vol. 18, No. 20

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Received 23 April 2023

Accepted 21 August 2023

Published online 10 October 2023

Published in print August 2023

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To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2023-0120

Financial disclosure

The study was partly supported by the National Institute of Health/National Institute of Neurological Disorders and Stroke R03 grant (R03NS112078). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

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Lipid nanocarrier targeting activated macrophages for antiretroviral therapy of HIV reservoir

Abstract

Plain language summary

References