期刊
ACS APPLIED MATERIALS & INTERFACES
卷 14, 期 2, 页码 2488-2500出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c17415
关键词
lipid-coated polymer nanoparticles; biomimicry; HIV-1; bio-nano interface; GM3
资金
- National Institutes of Health [S10OD024993, R01AI132111, R01AI064099, P30AI042853, R01CA138509]
- Immunology Training Program [T32 AI-007309]
- Boston University Micro and Nano Imaging Facility
- Office of The Director
In this study, GM3-presenting lipid-coated polymer nanoparticles were developed as carriers for sustained release of two antiretroviral drugs, leading to sustained inhibition of HIV-1 infection. The nanoparticles demonstrated favorable release properties and their intracellular localization correlated with retention of drug concentrations and sustained inhibition of viral infection. This work highlights the potential of lipid-coated polymer nanoparticles to eradicate viral reservoirs or achieve long-lasting prophylaxis against HIV-1 infection.
Monosialodihexosylganglioside ( GM3)-presenting lipid-coated polymer nanoparticles (NPs) that recapitulate the sequestration of human immunodeficiency virus-1 (HIV-1) particles in CD169(+) virus-containing compartments (VCCs) of macrophages were developed as carriers for delivery and sustained release of a combination of two antiretrovirals (ARVs), rilpivirine (RPV) and cabotegravir (CAB). RPV and CAB were co-loaded into GM3-presenting lipid-coated polylactic acid (PLA) and poly(lactic-co-glycolic acid) (PLGA) NPs without loss in potency of the drugs. GM3-presenting PLA NPs demonstrated the most favorable release properties and achieved inhibition of HIV-1 infection of primary human macrophages for up to 35 days. Intracellular localization of GM3-presenting PLA NPs in VCCs correlated with retention of intracellular ARV concentrations and sustained inhibition of HIV-1 infection. This work elucidates the design criteria of lipid-coated polymer NPs to utilize CD169(+) macrophages as cellular drug depots for eradicating the viral reservoir sites or to achieve long-acting prophylaxis against HIV-1 infection.
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