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1.
Adv Nanobiomed Res ; 2(5)2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-36313942

RESUMO

Herein, lipid-coated mesoporous silica nanoparticles (LMSN) are investigated as biomimetic delivery vehicle for two antiretroviral compounds (ARVs), rilpivirine (RPV) and cabotegravir (CAB). Monosialodihexosylganglioside (GM3) is incorporated into the membrane to facilitate LMSN binding to CD169 (Siglec-1)-expressing myeloid cells, that are predominantly expressed in secondary lymphoid tissues in vivo. It is demonstrated that in addition to providing CD169-binding functionalities, the lipid membrane around the silica core provides stealth properties that dampen the inflammatory cytokine response to ARVs-loaded LMSN in human monocyte-derived macrophages. Quantification of RPV and CAB releases from nanoparticles, and assessment of antiviral potency to human immunodeficiency virus (HIV-1) infection in vitro reveals that RPV and CAB co-formulated into LMSN retain optimal antiviral potency for 90 days, even upon storage at room temperature, making LMSN an attractive nanoplatform, immune to cold chain requirements. These findings suggest that GM3-LMSN equip the mesoporous silica nanoparticle (MSN) core with lipid-derived properties for surface passivation and lipid-mediated binding that are of high interest for achieving an effective delivery of ARVs to tissue reservoirs of HIV-1 replication.

2.
ACS Appl Mater Interfaces ; 14(2): 2488-2500, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34995059

RESUMO

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.


Assuntos
Fármacos Anti-HIV/farmacologia , Materiais Biocompatíveis/química , Dicetopiperazinas/farmacologia , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Piridonas/farmacologia , Rilpivirina/farmacologia , Fármacos Anti-HIV/química , Dicetopiperazinas/química , Portadores de Fármacos/química , Humanos , Lipossomos/química , Macrófagos/efeitos dos fármacos , Macrófagos/virologia , Teste de Materiais , Testes de Sensibilidade Microbiana , Nanopartículas/química , Poliésteres/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Piridonas/química , Rilpivirina/química , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/antagonistas & inibidores
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