Pharmaceutical Vehicles for Vaginal and Rectal Administration of Anti-HIV Microbicide Nanosystems

Abstract

Prevention strategies play a key role in the fight against HIV/AIDS. Vaginal and rectal microbicides hold great promise in tackling sexual transmission of HIV-1, but effective and safe products are yet to be approved and made available to those in need. While most efforts have been placed in finding and testing suitable active drug candidates to be used in microbicide development, the last decade also saw considerable advances in the design of adequate carrier systems and formulations that could lead to products presenting enhanced performance in protecting from infection. One strategy demonstrating great potential encompasses the use of nanosystems, either with intrinsic antiviral activity or acting as carriers for promising microbicide drug candidates. Polymeric nanoparticles, in particular, have been shown to be able to enhance mucosal distribution and retention of promising antiretroviral compounds. One important aspect in the development of nanotechnology-based microbicides relates to the design of pharmaceutical vehicles that allow not only convenient vaginal and/or rectal administration, but also preserve or even enhance the performance of nanosystems. In this manuscript, we revise relevant work concerning the selection of vaginal/rectal dosage forms and vehicle formulation development for the administration of microbicide nanosystems. We also pinpoint major gaps in the field and provide pertinent hints for future work.

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

“…Nevertheless, vaginal discs would capture the volume of fluid already present in the vagina to form a gel, so the formulation would not result in an additional volume in the vaginal environment. This behaviour is similar to that already observed in vaginal films [67]. In addition, the volume the discs capture-as observed in the swelling test-would be lower than 2 mL, so the volume can be considered acceptable.…”

Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention

“…The use of a hydrogel as a dosage form for TDF-loaded liposomes and FTC may help overcome vaginal retention issues and allow comfortable self-administration by women [64]. The pharmaceutical performance of hydrogels regarding in loco retention and spreading are well known to be partially determined by the viscoelastic properties of hydrogels, and thus, rheological characterization provides important data [65].…”

The Antimicrobial Properties of Chitosan Can Be Tailored by Formulation

“…A further challenge is sufficient residence time within the vaginal cavity. Formulations such as liposomes-in-hydrogel formulations can assure the required mucoadhesive properties and vaginal residence time [13][14][15]. A liposomes-in-hydrogel formulation can exhibit a synergic effect; poorly soluble active substances/drugs will be incorporated in liposomes whereas the extend residence time within the vaginal site will be assured by hydrogel as a vehicle [16,17].…”