scholarly journals Smart Freeze-Dried Bigels for the Prevention of the Sexual Transmission of HIV by Accelerating the Vaginal Release of Tenofovir during Intercourse

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 232 ◽  
Author(s):  
Araceli Martín-Illana ◽  
Fernando Notario-Pérez ◽  
Raúl Cazorla-Luna ◽  
Roberto Ruiz-Caro ◽  
María Dolores Veiga
Keyword(s):  
Controlled Release ◽  
Seminal Fluid ◽  
Sexual Transmission ◽  
Antiretroviral Drugs ◽  
African Women ◽  
Vaginal Fluid ◽  
Freeze Dried ◽  
Route Of Transmission ◽  
Sub Saharan ◽  
Sexual Transmission Of Hiv

Sub-Saharan African women are still at risk from the human immunodeficiency virus (HIV), and sex with men is the main route of transmission. Vaginal formulations containing antiretroviral drugs are promising tools to give women the power to protect themselves. The aim of this work was to obtain freeze-dried bigels containing pectin, chitosan, or hypromellose for the vaginal controlled release of Tenofovir, which is accelerated in the presence of semen. Nine batches of bigels were formulated using different proportions of these polymers in the hydrogel (1, 2, and 3% w/w). The bigels obtained were freeze-dried and then underwent hardness and deformability, mucoadhesion, swelling, and drug release tests, the last two in simulated vaginal fluid (SVF) and SVF/simulated seminal fluid (SSF) mixture. The formulation containing 3% pectin (fd3P) has the highest values for hardness, resistance to deformation, and good mucoadhesivity. Its swelling is conditioned by the pH of the medium, which is responsive to the controlled release of Tenofovir in SVF, with the fastest release in the SVF/SSF mixture. fd3P would be an interesting smart microbicidal system to allow faster release of Tenofovir in the presence of semen, and thus increase women’s ability to protect themselves from the sexual transmission of HIV.

scholarly journals Dapivirine Bioadhesive Vaginal Tablets Based on Natural Polymers for the Prevention of Sexual Transmission of HIV

Polymers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 483 ◽  
Author(s):  
Raúl Cazorla-Luna ◽  
Araceli Martín-Illana ◽  
Fernando Notario-Pérez ◽  
Luis-Miguel Bedoya ◽  
Paulina Bermejo ◽  
...  
Keyword(s):  
Sexual Transmission ◽  
Vaginal Fluid ◽  
Natural Polymers ◽  
Vaginal Microbicides ◽  
Realistic Option ◽  
Sub Saharan ◽  
Sexual Transmission Of Hiv ◽  
Prevention Of Sexual Transmission ◽  
Exposure Prophylaxis ◽  
Self Protection

Young sub-Saharan women are a group that is vulnerable to the sexual transmission of HIV. Pre-exposure prophylaxis through vaginal microbicides could provide them an option for self-protection. Dapivirine has been demonstrated to have topical inhibitory effects in HIV, and to provide protection against the sexual transmission of this virus. This paper reports on the studies into swelling behaviour, bioadhesion and release carried out on dapivirine tablets based on chitosan, locust bean gum and pectin, to select the most suitable formulation. The modified simulated vaginal fluid led to a high solubility of dapivirine and allowed the dapivirine release profiles to be characterized in sink conditions; this aqueous medium is an alternative to organic solvents, which are not a realistic option when evaluating systems whose behaviour varies in aqueous and organic media. Of the formulations evaluated, dapivirine/pectin tablets containing 290 mg of polymer and 30 mg of dapivirine present the most moderate swelling, making them the most comfortable dosage forms. Their high bioadhesive capacity would also allow the formulation to remain in the action zone and release the drug in a sustained manner, pointing to this formulation as the most promising candidate for future evaluations of vaginal microbicides for the prevention of HIV.

scholarly journals Influence of Chitosan Swelling Behaviour on Controlled Release of Tenofovir from Mucoadhesive Vaginal Systems for Prevention of Sexual Transmission of HIV

Marine Drugs ◽  
2017 ◽  
Vol 15 (2) ◽  
pp. 50 ◽  
Author(s):  
Fernando Notario-Pérez ◽  
Araceli Martín-Illana ◽  
Raúl Cazorla-Luna ◽  
Roberto Ruiz-Caro ◽  
Luis-Miguel Bedoya ◽  
...  
Keyword(s):  
Controlled Release ◽  
Sexual Transmission ◽  
Swelling Behaviour ◽  
Sexual Transmission Of Hiv ◽  
Prevention Of Sexual Transmission

scholarly journals Chitosan-Based Mucoadhesive Vaginal Tablets for Controlled Release of the Anti-HIV Drug Tenofovir

Pharmaceutics ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 20 ◽  
Author(s):  
Raúl Cazorla-Luna ◽  
Fernando Notario-Pérez ◽  
Araceli Martín-Illana ◽  
Roberto Ruiz-Caro ◽  
Aitana Tamayo ◽  
...  
Keyword(s):  
Sexual Transmission ◽  
Microstructural Characterization ◽  
Vaginal Fluid ◽  
Vaginal Mucosa ◽  
Vaginal Microbicides ◽  
Polyelectrolyte Complexes ◽  
Antiretroviral Drug ◽  
Sexual Transmission Of Hiv ◽  
Self Protection

Vaginal microbicides have the potential to give women at high risk of contracting HIV the option of self-protection by preventing the sexual transmission of the virus. In this paper, mucoadhesive vaginal tablets based on chitosan, alone and in combination with pectin and locust bean gum, were developed for the sustained release of tenofovir (an antiretroviral drug). The formulations were placed in simulant vaginal fluid (SVF) to swell, and Hg porosity and SEM microscopy were used for the microstructural characterization of the swelling witnesses. The results show that the association of pectin and chitosan generated polyelectrolyte complexes and produced a robust system able to maintain its structure during the swelling process, when small pores are formed. Drug release and bovine vaginal mucoadhesion studies were performed in SVF showing that tenofovir-controlled dissolution profiles and adhesion to the mucosa were conditioned by the swelling processes of the polymer/s in each formulation. Tablets based on chitosan/pectin have the most homogeneous tenofovir dissolution profiles and last up to 96 h, remaining attached to the vaginal mucosa for the same period. These formulations can therefore be considered a good option for the self-protection of women from the sexual transmission of HIV.

HIV infections in sub-Saharan Africa not explained by sexual or vertical transmission

2002 ◽  
Vol 13 (10) ◽  
pp. 657-666 ◽  
Author(s):  
David Gisselquist ◽  
Richard Rothenberg ◽  
John Potterat ◽  
Ernest Drucker
Keyword(s):  
Hiv Transmission ◽  
Sexual Transmission ◽  
Hiv Infections ◽  
Developed Countries ◽  
Sub Saharan Africa ◽  
African Women ◽  
Heterosexual Transmission ◽  
Direction Of Causation ◽  
Sub Saharan ◽  
Hiv Negative

An expanding body of evidence challenges the conventional hypothesis that sexual transmission is responsible for more than 90% of adult HIV infections in Africa. Differences in epidemic trajectories across Africa do not correspond to differences in sexual behaviour. Studies among African couples find low rates of heterosexual transmission, as in developed countries. Many studies report HIV infections in African adults with no sexual exposure to HIV and in children with HIV-negative mothers. Unexplained high rates of HIV incidence have been observed in African women during antenatal and postpartum periods. Many studies show 20%–40% of HIV infections in African adults associated with injections (though direction of causation is unknown). These and other findings that challenge the conventional hypothesis point to the possibility that HIV transmission through unsafe medical care may be an important factor in Africa's HIV epidemic. More research is warranted to clarify risks for HIV transmission through health care.

scholarly journals A Novel CXCR4 Targeting Protein SDF-1/54 as an HIV-1 Entry Inhibitor

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 874 ◽  
Author(s):  
Suiyi Tan ◽  
Wenjuan Li ◽  
Zhaofeng Li ◽  
Yujing Li ◽  
Jiangyan Luo ◽  
...  
Keyword(s):  
Seminal Fluid ◽  
Therapeutic Potential ◽  
Infectious Clone ◽  
Antiretroviral Drugs ◽  
Entry Inhibitor ◽  
Target Cells ◽  
Vaginal Fluid ◽  
Functional Region ◽  
Anti Hiv ◽  
Hiv 1

CXC chemokine receptor 4 (CXCR4) is a co-receptor for HIV-1 entry into target cells. Its natural ligand, the chemokine SDF-1, inhibits viral entry mediated by this receptor. However, the broad expression pattern of CXCR4 and its critical roles in various physiological and pathological processes indicate that the direct application of SDF-1 as an entry inhibitor might have severe consequences. Previously, we constructed an effective SDF-1 mutant, SDF-1/54, by deleting the α-helix of the C-terminal functional region of SDF-1. Of note, SDF-1/54 shows remarkable decreased chemotoxic ability, but maintains a similar binding affinity to CXCR4, suggesting SDF-1/54 might better serve as a CXCR4 inhibitor. Here, we found that SDF-1/54 exhibited potent antiviral activity against various X4 HIV-1 strains, including the infectious clone HIV-1 NL4-3, laboratory-adapted strain HIV-1 IIIB, clinical isolates and even drug-resistant strains. By using time-of-addition assay, non-infectious and infectious cell–cell fusion assay and CXCR4 internalization assay, we demonstrated SDF-1/54 is an HIV-1 entry inhibitor. A combination of SDF-1/54 with several antiretroviral drugs exhibited potent synergistic anti-HIV-1 activity. Moreover, SDF-1/54 was stable and its anti-HIV-1 activity was not significantly affected by the presence of seminal fluid, vaginal fluid simulant and human serum albumin. SDF-1/54 showed limited in vitro cytotoxicity to lymphocytes and vaginal epithelial cells. Based on these findings, SDF-1/54 could have a therapeutic potential as an HIV-1 entry inhibitor.

scholarly journals The High Content of Fructose in Human Semen Competitively Inhibits Broad and Potent Antivirals That Target High-Mannose Glycans

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Jacklyn Johnson ◽  
Manuel G. Flores ◽  
John Rosa ◽  
Changze Han ◽  
Alicia M. Salvi ◽  
...  
Keyword(s):  
Seminal Plasma ◽  
Seminal Fluid ◽  
Cell Attachment ◽  
Sexual Transmission ◽  
Antiviral Agents ◽  
High Concentration ◽  
Human Seminal Plasma ◽  
Sexual Transmission Of Hiv ◽  
Hiv 1

ABSTRACT Semen is the primary transmission vehicle for various pathogenic viruses. Initial steps of transmission, including cell attachment and entry, likely occur in the presence of semen. However, the unstable nature of human seminal plasma and its toxic effects on cells in culture limit the ability to study in vitro virus infection and inhibition in this medium. We found that whole semen significantly reduces the potency of antibodies and microbicides that target glycans on the envelope glycoproteins (Envs) of HIV-1. The extraordinarily high concentration of the monosaccharide fructose in semen contributes significantly to the effect by competitively inhibiting the binding of ligands to α1,2-linked mannose residues on Env. Infection and inhibition in whole human seminal plasma are accurately mimicked by a stable synthetic simulant of seminal fluid that we formulated. Our findings indicate that, in addition to the protein content of biological secretions, their small-solute composition impacts the potency of antiviral microbicides and mucosal antibodies. IMPORTANCE Biological secretions allow viruses to spread between individuals. Each type of secretion has a unique composition of proteins, salts, and sugars, which can affect the infectivity potential of the virus and inhibition of this process. Here, we describe HIV-1 infection and inhibition in whole human seminal plasma and a synthetic simulant that we formulated. We discovered that the sugar fructose in semen decreases the activity of a broad and potent class of antiviral agents that target mannose sugars on the envelope protein of HIV-1. This effect of semen fructose likely reduces the efficacy of such inhibitors to prevent the sexual transmission of HIV-1. Our findings suggest that the preclinical evaluation of microbicides and vaccine-elicited antibodies will be improved by their in vitro assessment in synthetic formulations that simulate the effects of semen on HIV-1 infection and inhibition.

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