Enfuvirtide-Protoporphyrin IX Dual-Loaded Liposomes: In Vitro Evidence of Synergy against HIV-1 Entry into Cells.
ACS Infect Dis
; 6(2): 224-236, 2020 02 14.
Article
in En
| MEDLINE
| ID: mdl-31855415
ABSTRACT
We have developed a nanocarrier consisting of large unilamellar vesicles (LUVs) for combined delivery of two human immunodeficiency virus type 1 (HIV-1) entry inhibitors, enfuvirtide (ENF) and protoporphyrin IX (PPIX). The intrinsic lipophilicity of ENF and PPIX, a fusion inhibitor and an attachment inhibitor, respectively, leads to their spontaneous incorporation into the lipid bilayer of the LUVs nanocarrier. Both entry inhibitors partition significantly toward LUVs composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and a 91 mixture of POPC1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DPPE-PEG2000), representative of conventional and immune-evasive drug delivery formulations, respectively. These colocalize in the core of lipid membranes. Dual-loaded nanocarriers are monodispersed and retain the size distribution, thermotropic behavior, and surface charge of the unloaded form. Combination of the two entry inhibitors in the nanocarrier resulted in improved synergy against HIV-1 entry compared to combination in free form, strongly when immune-evasive formulations are used. We propose that the improved action of the entry inhibitors when loaded into the nanocarriers results from their slow release at the site of viral entry. Overall, liposomes remain largely unexplored platforms for combination of viral entry inhibitors, with potential for improvement of current antiretroviral therapy drug safety and application. Our work calls for a reappraisal of the potential of entry inhibitor combinations and delivery for clinical use in antiretroviral therapy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protoporphyrins
/
HIV-1
/
Virus Internalization
/
Enfuvirtide
Limits:
Humans
Language:
En
Journal:
ACS Infect Dis
Year:
2020
Document type:
Article
Affiliation country: