Intravaginal rings as delivery systems for microbicides and multipurpose prevention technologies

Abstract

There is a renewed interest in delivering pharmaceutical products via intravaginal rings (IVRs). IVRs are flexible torus-shaped drug delivery systems that can be easily inserted and removed by the woman and that provide both sustained and controlled drug release, lasting for several weeks to several months. In terms of women’s health care products, it has been established that IVRs effectively deliver contraceptive steroids and steroids for the treatment of postmenopausal vaginal atrophy. A novel application for IVRs is the delivery of antiretroviral drugs for the prevention of human immunodeficiency virus (HIV) genital infection. Microbicides are antiviral drugs delivered topically for HIV prevention. Recent reviews of microbicide IVRs have focused on technologies in development and optimizing ring design. IVRs have several advantages, including the ability to deliver sustained drug doses for long periods of time while bypassing first pass metabolism in the gut. IVRs are discreet, woman-controlled, and do not require a trained provider for placement or fitting. Previous data support that women and their male sexual partners find IVRs highly acceptable. Multipurpose prevention technology (MPT) products provide protection against unintended/mistimed pregnancy and reproductive tract infections, including HIV. Several MPT IVRs are currently in development. Early clinical testing of new microbicide and MPT IVRs will require a focus on safety, pharmacokinetics and pharmacodynamics. Specifically, IVRs will have to deliver tissue concentrations of drugs that are pharmacodynamically active, do not cause mucosal alterations or inflammation, and do not change the resident microbiota. The emergence of resistance to antiretrovirals will need to be investigated. IVRs should not disrupt intercourse or have high rates of expulsion. Herein, we reviewed the microbicide and MPT IVRs currently in development, with a focus on the clinical aspects of IVR assessment and the challenges facing microbicide and MPT IVR product development, clinical testing, and implementation. The information in this review was drawn from PubMed searches and a recent microbicide/MPT product development workshop organized by CONRAD.

MIV-150-Containing Intravaginal Rings Protect Macaque Vaginal Explants against SHIV-RT Infection

“…ntravaginal rings (IVRs) represent a promising approach to deliver anti-HIV microbicides with the premise to provide optimal drug concentrations for protection over a month or longer and to potentially improve adherence (1)(2)(3)(4)(5)(6)(7). Several IVRs are currently in different stages of development (5,8).…”

Griffithsin-Modified Electrospun Fibers as a Delivery Scaffold To Prevent HIV Infection

“…In comparison to gels and intravaginal films, IVRs currently provide the "gold standard" for sustained release and have been demonstrated to deliver contraceptives and provide long-term protection against STIs for over 90 days (80)(81)(82). The ASPIRE and IPM trials recently demonstrated the feasibility of dapivirine IVRs as PrEP against HIV, resulting in a decrease in the rate of HIV infection by 27% and 31%, respectively, for up to 1 month (83).…”

Pharmaceutical-technological aspects of therapeutic systems for hormonal contraception

“…S obzirom da je rizik od neplanirane trudnoće istovremeno i rizik od infekcija prenosivih seksualnim putem, već dve decenije brojne organizacije, institucije od javnog značaja i farmaceutske kompanije, prevenstveno iz SAD, ulažu značajna finansijska sredstva za intenziviranje razvoja vaginalnih prstenova kao tehnologije za višenamensku prevenciju (Multipurpose prevention technologies, MPT) začeća i infekcija virusom humane imunodeficijencije (human immunodeficiency virus, HIV) i Herpes virusima [60]. Prema zvaničnom statističkom izveštaju iz 2015. godine ukupan broj inficiranih HIV-om na globalnom nivou iznosi 36,7 miliona, pri čemu je u poslednjih godinu dana broj povećan za oko 2,1 milion [61].…”

“…Prva faza kliničkih ispitivanja započela je 2015. godine. Od posebnog značaja je procena njegove pogodnosti da se oslobođenim tenofovirom ostvari antimikrobno delovanje u području primene, uz zanemarljivu sistemsku isporuku kako bi se smanjio rizik od razvoja rezistencije na antiretrovirotike, što je uobičajeno kada se primenjuju per os [60].…”