Penetration of polymeric nanoparticles loaded with an HIV-1 inhibitor peptide derived from GB virus C in a vaginal mucosa model

Abstract

Despite the great effort to decrease the HIV infectivity rate, current antiretroviral therapy has several weaknesses; poor bioavailability, development of drug resistance and poor ability to access tissues. However, molecules such as peptides have emerged asa new expectative to HIV eradication. The vaginal mucosa is the main spreading point of HIV. There are natural barriers such as the vaginal fluid which protects the vaginal epithelium from any foreign agents reaching it. This work has developed and characterized Nanoparticles (NPs) coated with glycol chitosan (GC), loaded with an HIV-1 inhibitor peptide (E2). In vitro release and ex vivo studies were carried out using the vaginal mucosa of swine and the peptide was determined by HPLC MS/MS validated method. Moreover, the peptide was labeled with 5(6)-carboxyfluoresceine and entrapped into the NPs to carried out in vivo studies and to evaluate the NPs penetration and toxicity in the vaginal mucosa of the swine. The mean size of the NPs, ξ and the loading percentage were fundamental features for to reach the vaginal tissue and to release the peptide within intercellular space. The obtained results suggesting that the fusion inhibitor peptides loaded into the NPs coated with GC might be a new way to fight the HIV-1, due to the formulation might reach the human epithelial mucosa and release peptide without any side effects.

Design, Characterization, and Biopharmaceutical Behavior of Nanoparticles Loaded with an HIV-1 Fusion Inhibitor Peptide

“…These measurements were performed on samples stored for up to 7 days at 4 ºC. The experiments were performed following the protocol described by das Neves et al 16 Permeation studies were carried out following the protocol described in Ariza-Sáenz et al, 37 . A mixture of receptor medium and Transcutol P ® (80:20, v/v) was placed in the receptor compartment, each assay was performed in triplicate.…”

Dexibuprofen Biodegradable Nanoparticles: One Step Closer towards a Better Ocular Interaction Study

“…Nanocarriers are particularly attractive as they provide protection to the drug, increase drug efficacy, permeate physiological barriers and decrease toxicity [1]. In this sense, biodegradable nanoparticles made of poly-D,L-lactic-co-glycolic acid (PLGA) may represent a suitable candidate to encapsulate DXI and deliver it slowly into the target tissue [4]. In addition, PLGA has been approved by the Food and Drug Administration and is one of the most successful biodegradable polymers [3][4][5][6].…”

“…In this sense, biodegradable nanoparticles made of poly-D,L-lactic-co-glycolic acid (PLGA) may represent a suitable candidate to encapsulate DXI and deliver it slowly into the target tissue [4]. In addition, PLGA has been approved by the Food and Drug Administration and is one of the most successful biodegradable polymers [3][4][5][6]. Moreover, PEG has been widely used to reduce the clearance of PLGA nanoparticles (NPs) and it has been demonstrated that PEG coatings shield the surface from aggregation, opsonization, phagocytosis and prolong nanoparticles systemic circulation time [5].…”

Approaches in Polymeric Nanoparticles for Vaginal Drug Delivery: A Review of the State of the Art

“…PEG nanoparticles, which have a neutral surface, can penetrate the mucosal epithelium more efficiently, and mucoadhesive Avid-NP do not undergo leakage to the same extent as unmodified PLGA nanoparticles. It is important to remark that the porcine vaginal mucosa and the human vaginal mucosa consisted of stratified squamous epithelium supported by connective tissue and of the lamina propria, and they have a similar lipid composition, important for barrier function [ 44 , 56 ].…”

“…Recently, Ariza-Sáenz et al [ 44 ] prepared PLGA nanoparticles covered with glycol-chitosan and loaded with an HIV fusion inhibitor peptide (E2) and evaluated their ex vivo penetration in vaginal mucosa and their in vivo penetration rate in female swine. Nanoparticles with E2 (E2-NP) and 5(6)-carboxyfluorescein (E2-FAM-NP) as well as empty nanoparticles were obtained by a modified double-emulsion method and were covered with chitosan conjugated with ethylene glycol.…”