ArticleAIDS (London, England)2012
Long-acting nanoformulated antiretroviral therapy elicits potent antiretroviral and neuroprotective responses in HIV-1-infected humanized mice.
Article in AIDS (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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Who cites it
79 citing papers in PubMed, 131 citations in OpenAlex.
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- Lipid nanocarrier targeting activated macrophages for antiretroviral therapy of HIV reservoir.Nanomedicine (London, England) · 2023Article
- Preclinical Evaluation of Long-Acting Emtricitabine Semi-Solid Prodrug Nanoparticle Formulations.Pharmaceutics · 2023Article
- CRISPR editing of CCR5 and HIV-1 facilitates viral elimination in antiretroviral drug-suppressed virus-infected humanized mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Nanotechnology advances in pathogen- and host-targeted antiviral delivery: multipronged therapeutic intervention for pandemic control.Drug delivery and translational research · 2021Review
- Humanized Mice for Infectious and Neurodegenerative disorders.Retrovirology · 2021Review
- HIV-1 and drug abuse comorbidity: Lessons learned from the animal models of NeuroHIV.Neuroscience letters · 2021Review
- Nanoparticle delivery system, highly active antiretroviral therapy, and testicular morphology: The role of stereology.Pharmacology research & perspectives · 2021Review
- Review
- Cancer stem cells and macrophages: molecular connections and future perspectives against cancer.Oncotarget · 2021Review
- HIV-1-Associated Left Ventricular Cardiac Dysfunction in Humanized Mice.Scientific reports · 2020Article
- A Comparative Study of the Effect of Different Stabilizers on the Critical Quality Attributes of Self-Assembling Nano Co-Crystals.Pharmaceutics · 2020Article
- Nose to brain delivery of antiretroviral drugs in the treatment of neuroAIDS.Molecular biomedicine · 2020Review
- Amplification of Replication Competent HIV-1 by Adoptive Transfer of Human Cells From Infected Humanized Mice.Frontiers in cellular and infection microbiology · 2020Article
- Establishment of the Dual Humanized TK-NOG Mouse Model for HIV-associated Liver Pathogenesis.Journal of visualized experiments : JoVE · 2019Article
- Nanotechnology approaches for delivery of cytochrome P450 substrates in HIV treatment.Expert opinion on drug delivery · 2019Review
- Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice.Nature communications · 2019Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesLong-acting nanoformulated antiretroviral therapy (nanoART) with improved pharmacokinetics, biodistribution and limited systemic toxicities will likely improve drug adherence and access to viral reservoirs.
designAtazanavir and ritonavir crystalline nanoART were formulated in a poloxamer-188 excipient by high-pressure homogenization. These formulations were evaluated for antiretroviral and neuroprotective activities in humanized NOD/scid-IL-2Rgc (NSG) mice.
methodsNanoART-treated NSG mice were evaluated for drug biodistribution, pharmacodynamics and toxicity. CD34 human hematopoietic stem cells were transplanted at birth in replicate NSG mice. The mice were infected with HIV-1ADA at 5 months of age. Eight weeks later, the infected animals were treated with weekly subcutaneous injections of nanoformulated ATV and RTV. Peripheral viral load, CD4 T-cell counts and lymphoid and brain histopathology and immunohistochemistry tests were performed.
resultsNanoART treatments by once-a-week injections reduced viral loads more than 1000-fold and protected CD4 T-cell populations. This paralleled high ART levels in liver, spleen and blood that were in or around the human minimal effective dose concentration without notable toxicities. Importantly, examination of infected brain subregions showed that nanoART elicited neuroprotective responses with detectable increases in microtubule-associated protein-2, synaptophysin and neurofilament expression when compared to untreated virus-infected animals. Therapeutic interruptions produced profound viral rebounds.
conclusionLong-acting nanoART has translational potential with sustained and targeted efficacy and with limited systemic toxicities. Such success in drug delivery and distribution could improve drug adherence and reduce viral resistance in infected people.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.