CCR5-ligand decorated rilpivirine lipid-based nanoparticles for sustained antiretroviral responses

Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART effectiveness and leads to immune compromise, viral mutations, and disease co-morbidities. Here we develop a drug formulation in whi...

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Bibliographic Details
Published in:Nature communications 2025-01, Vol.16 (1), p.513-14, Article 513
Main Authors: Patel, Milankumar, Panja, Sudipta, Zaman, Lubaba A., Yeapuri, Pravin, Bhattarai, Shaurav, Gorantla, Santhi, Chang, Linda, Heredia, Alonso, Walczak, Piotr, Hanson, Brandon, Cohen, Samuel M., Kevadiya, Bhavesh D., Gendelman, Howard E.
Format: Article
Language:English
Subjects:
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14/19
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Antiretroviral agents
Antiretroviral drugs
Antiretroviral therapy
Blood-brain barrier
CC chemokine receptors
Chemokine receptors
HIV
Human immunodeficiency virus
Humanities and Social Sciences
Lipids
Macrophages
Monocytes
multidisciplinary
Myeloid cells
Nanoparticles
Positron emission
Positron emission tomography
Quality of life
Science
Science (multidisciplinary)
Ultrasonic imaging
Ultrasound
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Summary:Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART effectiveness and leads to immune compromise, viral mutations, and disease co-morbidities. Here we develop a drug formulation in which a lipid-based nanoparticle (LBNP) carrying rilpivirine (RPV) is decorated with the C-C chemokine receptor type 5 (CCR5) targeting peptide. This facilitates extended drug persistence within myeloid cells. Particle delivery to viral reservoirs is tracked by positron emission tomography. The CCR5-mediated LBNP cell uptake and retention reduce HIV-1 replication in human monocyte-derived macrophages and infected humanized mice (hu mice). Focused ultrasound with microbubbles mediated blood brain barrier (BBB) disruption allows the CCR5-targeted LBNP to penetrate the BBB and reach brain myeloid cells. These findings offer a role for CCR5-targeted therapeutics in antiretroviral delivery to optimize HIV suppression. Here the authors made lipid-based CCR5-receptor targeted nanoparticles to facilitate cell-based delivery of the antiretroviral drug rilpivirine, improving HIV-1 suppression in cell and tissue reservoirs. Focused ultrasound facilitates penetrance of the nanoparticles across the blood-brain barrier where they enter myeloid cells in humanized mice.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-55544-9