Macrophage folate receptor-targeted antiretroviral therapy facilitates drug entry, retention, antiretroviral activities and biodistribution for reduction of human immunodeficiency virus infections
| Autor: | Ram S. Veerubhotla, Alexander V. Kabanov, Shantanu Balkundi, Xin Ming Liu, Howard E. Gendelman, Lindsey M. Kendrick, JoEllyn M McMillan, Tatiana K. Bronich, Pavan Puligujja, Nathan Smith, Benson J Edagwa, Tianyuzi Li |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Drug Biodistribution Anti-HIV Agents Pyridines media_common.quotation_subject Atazanavir Sulfate Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) HIV Infections Bioengineering Biology Article Mice Drug Delivery Systems Folic Acid Pharmacokinetics medicine Animals Humans Tissue Distribution General Materials Science Cells Cultured media_common Mice Inbred BALB C Nanoart Macrophages Folate Receptors GPI-Anchored Virology Atazanavir Targeted drug delivery Folate receptor HIV-1 Molecular Medicine Ritonavir Oligopeptides medicine.drug |
| Zdroj: | Nanomedicine: Nanotechnology, Biology and Medicine. 9:1263-1273 |
| ISSN: | 1549-9634 |
| DOI: | 10.1016/j.nano.2013.05.003 |
| Popis: | Macrophages serve as vehicles for the carriage and delivery of polymer-coated nanoformulated antiretroviral therapy (nanoART). Although superior to native drug, high drug concentrations are required for viral inhibition. Herein, folate-modified ritonavir-boosted atazanavir (ATV/r)-encased polymers facilitated macrophage receptor targeting for optimizing drug dosing. Folate coating of nanoART ATV/r significantly enhanced cell uptake, retention and antiretroviral activities without altering cell viability. Enhanced retentions of folate-coated nanoART within recycling endosomes provided a stable subcellular drug depot. Importantly, up to a five-fold enhanced plasma and tissue drug levels followed folate-coated formulation injection in mice. Folate polymer encased ATV/r improves nanoART pharmacokinetics bringing the technology one step closer to human use. From the Clinical Editor This team of authors describes a novel method for macrophage folate receptor-targeted antiretroviral therapy. Atazanvir entry, retention, and antiretroviral activities were superior using the presented method, and so was its biodistribution, enabling a more efficient way to address human immunodeficiency virus infections, with a hoped for clinical application in the near future. |
| Databáze: | OpenAIRE |
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