CCR5-ligand decorated rilpivirine lipid-based nanoparticles for sustained antiretroviral responses
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 formulati...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55544-9 |
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| Summary: | 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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| ISSN: | 2041-1723 |