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

Milankumar Patel; Sudipta Panja; Lubaba A. Zaman; Pravin Yeapuri; Shaurav Bhattarai; Santhi Gorantla; Linda Chang; Alonso Heredia; Piotr Walczak; Brandon Hanson; Samuel M. Cohen; Bhavesh D. Kevadiya; Howard E. Gendelman

doi:10.1038/s41467-024-55544-9

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

Milankumar Patel, Sudipta Panja, Lubaba A. Zaman, Pravin Yeapuri, Shaurav Bhattarai, Santhi Gorantla, Linda Chang, Alonso Heredia, Piotr Walczak, Brandon Hanson, Samuel M. Cohen, Bhavesh D. Kevadiya, Howard E. Gendelman

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	513
Journal	Nature communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-55544-9
State	Published - Dec 2025

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Patel, M., Panja, S., Zaman, L. A., Yeapuri, P., Bhattarai, S., Gorantla, S., Chang, L., Heredia, A., Walczak, P., Hanson, B., Cohen, S. M., Kevadiya, B. D., & Gendelman, H. E. (2025). CCR5-ligand decorated rilpivirine lipid-based nanoparticles for sustained antiretroviral responses. Nature communications, 16(1), Article 513. https://doi.org/10.1038/s41467-024-55544-9

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abstract = "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.",

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AU - Patel, Milankumar

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AU - Zaman, Lubaba A.

AU - Yeapuri, Pravin

AU - Bhattarai, Shaurav

AU - Gorantla, Santhi

AU - Chang, Linda

AU - Heredia, Alonso

AU - Walczak, Piotr

AU - Hanson, Brandon

AU - Cohen, Samuel M.

AU - Kevadiya, Bhavesh D.

AU - Gendelman, Howard E.

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N2 - 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.

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

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