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

Author

Listed:
  • 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
    Johns Hopkins University 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)

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.

Suggested Citation

  • 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., 2025. "CCR5-ligand decorated rilpivirine lipid-based nanoparticles for sustained antiretroviral responses," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55544-9
    DOI: 10.1038/s41467-024-55544-9
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