Lipid Vesicles Loaded with an HIV-1 Fusion Inhibitor Peptide as a Potential Microbicide

Abstract

The effective use of fusion inhibitor peptides against cervical and colorectal infections requires the development of sustained release formulations. In this work we comparatively study two different formulations based on polymeric nanoparticles and lipid vesicles to propose a suitable delivery nanosystem for releasing an HIV-1 fusion inhibitor peptide in vaginal mucosa. Polymeric nanoparticles of poly-d,l-lactic-co-glycolic acid (PLGA) and lipid large unilamellar vesicles loaded with the inhibitor peptide were prepared. Both formulations showed average sizes and polydispersity index values corresponding to monodisperse systems appropriate for vaginal permeation. High entrapment efficiency of the inhibitor peptide was achieved in lipid vesicles, which was probably due to the peptide’s hydrophobic nature. In addition, both nanocarriers remained stable after two weeks stored at 4 °C. While PLGA nanoparticles (NPs) did not show any delay in peptide release, lipid vesicles demonstrated favorably prolonged release of the peptide. Lipid vesicles were shown to improve the retention of the peptide on ex vivo vaginal tissue in a concentration sufficient to exert its pharmacological effect. Thus, the small size of lipid vesicles, their lipid-based composition as well as their ability to enhance peptide penetration on vaginal tissue led us to consider this formulation as a better nanosystem than polymeric nanoparticles for the sustained delivery of the HIV-1 fusion inhibitor peptide in vaginal tissues.

Peptide Amphiphilic-Based Supramolecular Structures with Anti-HIV-1 Activity

“…In our hands, the design of novel amphiphilic peptides made it possible to obtain peptide structures capable of self-assembly in aqueous solution, favoring the solubility of lipopeptides, based on the E1P47 sequence, which are highly hydrophobic and would be highly insoluble under physiological conditions. So far, we have studied the possible administration of entry inhibitor peptides incorporated into drug delivery systems such as liposomes or polymeric nanoparticles. − In the present work, we have designed an amphiphilic peptide with anti-HIV-1 activity that is capable of forming self-assembled nanostructures that could allow the administration of the inhibitor peptide without the need of its incorporation into a delivery vehicle.…”

“…So far, we have studied the possible administration of entry inhibitor peptides incorporated into drug delivery systems such as liposomes or polymeric nanoparticles. 42 − 45 In the present work, we have designed an amphiphilic peptide with anti-HIV-1 activity that is capable of forming self-assembled nanostructures that could allow the administration of the inhibitor peptide without the need of its incorporation into a delivery vehicle.…”

Biomedical application, drug delivery and metabolic pathway of antiviral nanotherapeutics for combating viral pandemic: A review

“…Niosomes, the non-ionic surfactant based liposome alike organic nanovesicle are getting popular in the advanced biomedical sciences considering their non-immunogenicity and stable optical properties, which make them a suitable carrier of both hydro/lipophilic drug molecules. Excellent bioavailability and controlled release of specific drugs at the targeted sites make such nanocarriers ideal antiviral agents (HSV-1 virus), where nano-niosome was loaded with suitable antiviral drug (acyclovir) ( Sánchez-López et al, 2020 ). Improved drug delivery mechanism and suitable drug release kinetics may allow such nanocarriers to be used in infectious virus diseases (nanomicelles) ( Fig.…”

Nanosystems Applied to HIV Infection: Prevention and Treatments

“…Sánchez–López et al prepared suitable delivery nanocarriers for releasing HIV-1 fusion inhibitor peptide in vaginal mucosa: polymeric NPs of PLGA and lipid large unilamellar vesicles loaded with the inhibitor peptide [ 67 ]. The authors comparatively studied both systems and found high entrapment efficiency of the inhibitor peptide in lipid vesicles, which was understood because of the hydrophobic nature of the peptide.…”