Mucoadhesive Vaginal Discs based on Cyclodextrin and Surfactants for the Controlled Release of Antiretroviral Drugs to Prevent the Sexual Transmission of HIV

Abstract

The strategies for developing vaginal microbicides to protect women against human immunodeficiency virus (HIV) sexual transmission are constantly changing. Although the initial dosage forms required daily administration to offer effective protection, the trend then moved towards sustained-release dosage forms that require less frequency of administration in order to improve women’s compliance with the treatment. Nevertheless, another possible strategy is to design on-demand products that can be used in a coitally-dependent manner and only need to be administered immediately before intercourse to offer protection. Vaginal discs based on freeze-dried hydroxypropylmethyl cellulose gels have been developed for this purpose, containing two surfactants, i.e., sodium dodecyl sulphate and polysorbate 60, alone or in combination with 2-hydroxypropyl-β-cyclodextrin, to achieve a formulation capable of incorporating both hydrophilic and lipophilic drugs. Several studies have been carried out to evaluate how the inclusion of these substances modifies the structure of gels (viscosity and consistency studies) and the porosimetry of the freeze-dried discs (scanning electron microscopy micrographs, mechanical properties, swelling behaviour). The drug release and mucoadhesive properties of the discs have also been evaluated with a view to their clinical application. The systems combining sodium dodecyl sulphate and 2-hydroxypropyl-β-cyclodextrin were found to be adequate for the vaginal administration of both Tenofovir and Dapivirine and also offer excellent mucoadhesion to vaginal tissue; these discs could therefore be an interesting option for a coitally-dependent administration to protect women against HIV transmission.

Technological evolution of cyclodextrins in the pharmaceutical field

“…However, other diseases, like those related to human papillomavirus, herpes simplex virus, and HIV, along with the unfortunate increase in the prevalence of cervix carcinoma, have recently driven the interest to develop vaginal formulations [ 134 ]. Several compelling investigations have shown that CDs are useful, as solubilizers, in the development of these type of formulations such as mucoadhesive gels, creams, and films for antifungal and antiviral activities [ [135] , [136] , [137] ]; gels for contraception purpose [ 138 ]; vaginal discs for the controlled delivery of antiretroviral drugs [ 139 ]; and mucoadhesive nanosystems for cervical cancer treatment [ 140 ]. Also studied are the mucoadhesive properties of CD derivatives in which CDs perse comprise the delivery systems [ 141 ].…”

Naturally Occurring Polyelectrolytes and Their Use for the Development of Complex-Based Mucoadhesive Drug Delivery Systems: An Overview

“…In the field of vaginal drug administration, we consider it especially important to highlight the efforts to develop formulations to prevent the sexual transmission of the human immunodeficiency virus (HIV). These dosage forms, known as vaginal microbicides, are considered an option for topical preexposure prophylaxis, which is a priority in the fight against HIV as directed by the Joint United Nations Programme on HIV and AIDS (UNAIDS) [ 96 , 154 ]. We developed tablets based on chitosan/pectin PECs for the vaginal controlled release of the anti-HIV drug tenofovir.…”

Contraception au futur

“…De même, un insert vaginal soluble, utilisé sous forme de tablette, se dissout au contact de la muqueuse vaginale pour former un gel à partir duquel une ou plusieurs molécules peuvent être libérées [31]. Ce type d'inserts ou ceux, solides, constitués de films bio-adhésifs, ont l'avantage d'éviter les écoulements vaginaux comme on les observe avec des gels vaginaux fluides [32,33]. Ils sont appréciés par les utilisatrices en raison de leur application qui reste discrète, de leur utilisation autonome, et de leur longue durée d'action [34].…”