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

Raúl Cazorla-Luna,Araceli Martín-Illana,María Dolores Veiga,Aitana Tamayo,Fernando Notario-Pérez,Juan Rubio,Roberto Ruiz-Caro

doi:10.3390/pharmaceutics11010020

Abstract

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.

Highlights

According to the Joint United Nations Programme on HIV and AIDS (UNAIDS) factsheet from July 2018, between 31.1 and 43.9 million people currently live with HIV, fewer than 23 million of them have access to antiretroviral therapy. 1.8 million people contracted the infection in 2017 indicating that, the transmission of the disease has fallen by 47% since 1996, the problem is still far from being solved
The development of effective systems to prevent HIV infection initiated by women themselves is a challenge that has yet to be solved, and pre-exposure prophylaxis (PrEP) is one of the most innovative tools for increasing the options for self-protection in the population at high risk of HIV infection [2,3]
Among the drugs used in vaginal microbicide development, reverse transcriptase inhibitors act on viral enzyme reverse transcriptase, which is responsible for transforming the viral RNA into DNA, inhibiting viral replication

Summary

Introduction

According to the Joint United Nations Programme on HIV and AIDS (UNAIDS) factsheet from July 2018, between 31.1 and 43.9 million people currently live with HIV, fewer than 23 million of them have access to antiretroviral therapy. 1.8 million people contracted the infection in 2017 indicating that, the transmission of the disease has fallen by 47% since 1996, the problem is still far from being solved. In Sub-Saharan Africa this group is twice as likely to live with HIV as men, and 75% of new infections occur in women aged 15–19 [1]. This high incidence of HIV in young women can be attributed to age-disparate sexual relationships, poor negotiating power with respect to the use of preventive tools (such as condoms) and intimate partner violence; the lack of prevention systems for women does not allow them to protect themselves from HIV transmission. It has been demonstrated that vaginal administration of TFV can achieve concentrations in vaginal tissue that are 130 times higher with an oral administration regimen [7]

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Conclusion