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 and Howard E. Gendelman ()
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Milankumar Patel: University of Nebraska Medical Center
Sudipta Panja: University of Nebraska Medical Center
Lubaba A. Zaman: University of Nebraska Medical Center
Pravin Yeapuri: University of Nebraska Medical Center
Shaurav Bhattarai: University of Nebraska Medical Center
Santhi Gorantla: University of Nebraska Medical Center
Linda Chang: University of Maryland School of Medicine
Alonso Heredia: University of Maryland School of Medicine
Piotr Walczak: University of Maryland School of Medicine
Brandon Hanson: University of Nebraska Medical Center
Samuel M. Cohen: University of Nebraska Medical Center
Bhavesh D. Kevadiya: University of Nebraska Medical Center
Howard E. Gendelman: University of Nebraska Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-024-55544-9

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