ArticleAntimicrobial agents and chemotherapy2012
Safe and sustained vaginal delivery of pyrimidinedione HIV-1 inhibitors from polyurethane intravaginal rings.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Dose-ranging pharmacokinetics, safety, and efficacy of a 90-day intravaginal ring delivering islatravir in pigtail macaques.Science advances · 2026Article
- Next-generation 3D printed multipurpose prevention intravaginal ring for prevention of HIV, HSV-2, and unintended pregnancy.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation.Bioengineering & translational medicine · 2024Article
- Refining the in vitro release test method for a dapivirine-releasing vaginal ring to match in vivo performance.Drug delivery and translational research · 2023Article
- The Vaginal Microbiota, Bacterial Biofilms and Polymeric Drug-Releasing Vaginal Rings.Pharmaceutics · 2021Review
- In Vitro Methods for Evaluating Drug Release of Vaginal Ring Formulations-A Critical Review.Pharmaceutics · 2019Review
- In situ-forming and pH-responsive hydrogel based on chitosan for vaginal delivery of therapeutic agents.Journal of materials science. Materials in medicine · 2018Article
- Effects of gel volume on pharmacokinetics for vaginal and rectal applications of combination DuoGel-IQB4012, a dual chamber-dual drug HIV microbicide gel, in pigtailed macaques.Drug delivery and translational research · 2018Article
- A Dose Ranging Pharmacokinetic Evaluation of IQP-0528 Released from Intravaginal Rings in Non-Human Primates.Pharmaceutical research · 2017Article
- Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIVJournal of medical primatology · 2017Article
- Evaluation of poly(lactic-co-glycolic acid) and poly(dl-lactide-co-ε-caprolactone) electrospun fibers for the treatment of HSV-2 infection.Materials science & engineering. C, Materials for biological applications · 2017Article
- Safety and Pharmacokinetics of Quick-Dissolving Polymeric Vaginal Films Delivering the Antiretroviral IQP-0528 for Preexposure Prophylaxis.Antimicrobial agents and chemotherapy · 2016Article
- Controlling the hydration rate of a hydrophilic matrix in the core of an intravaginal ring determines antiretroviral release.Journal of controlled release : official journal of the Controlled Release Society · 2016Article
- Pharmacokinetic and Pharmacodynamic Evaluation following Vaginal Application of IQB3002, a Dual-Chamber Microbicide Gel Containing the Nonnucleoside Reverse Transcriptase Inhibitor IQP-0528 in Rhesus Macaques.Antimicrobial agents and chemotherapy · 2015Article
- An Intravaginal Ring for the Simultaneous Delivery of an HIV-1 Maturation Inhibitor and Reverse-Transcriptase Inhibitor for Prophylaxis of HIV Transmission.Journal of pharmaceutical sciences · 2015Article
- Lack of in vitro-in vivo correlation for a UC781-releasing vaginal ring in macaques.Drug delivery and translational research · 2015Article
- Pharmacokinetic evaluation of tenofovir disoproxil fumarate released from an intravaginal ring in pigtailed macaques after 6 months of continuous use.Journal of medical primatology · 2014Article
- Pharmacokinetic and safety analyses of tenofovir and tenofovir-emtricitabine vaginal tablets in pigtailed macaques.Antimicrobial agents and chemotherapy · 2014Article
- Microbicides for the Treatment of Sexually Transmitted HIV Infections.Journal of pharmaceutics · 2014Review
- Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
The potent antiretroviral pyrimidinediones IQP-0528 (PYD1) and IQP-0532 (PYD2) were formulated in polyurethane intravaginal rings (IVRs) as prophylactic drug delivery systems to prevent the sexual transmission of HIV-1. To aid in the selection of a pyrimidinedione candidate and the optimal loading of the drug in the IVR delivery system, four pyrimidinedione IVR formulations (PYD1 at 0.5 wt% [PYD1(0.5 wt%)], PYD1(1 wt%), PYD2(4 wt%), and PYD2(14 wt%)) were evaluated in pigtail macaques over 28 days for safety and pyrimidinedione vaginal biodistribution. Kinetic analysis of vaginal proinflammatory cytokines, native microflora, and drug levels suggested that all formulations were safe, but only the high-loaded PYD2(14 wt%) IVR demonstrated consistently high pyrimidinedione vaginal fluid and tissue levels over the 28-day study. This formulation delivered drug in excess of 10 μg/ml to vaginal fluid and 1 μg/g to vaginal tissue, a level over 1,000 times the in vitro 50% effective concentration. The in vitro release of PYD1 and PYD2 under nonsink conditions correlated well with in vivo release, both in amount and in kinetic profile, and therefore may serve as a more biologically relevant means of evaluating release in vitro than typically employed sink conditions. Lastly, the pyrimidinediones in the IVR formulation were chemically stable after 90 days of storage at elevated temperature, and the potent nanomolar-level antiviral activity of both molecules was retained after in vitro release. Altogether, these results point to the successful IVR formulation and vaginal biodistribution of the pyrimidinediones and demonstrate the usefulness of the pigtail macaque model in evaluating and screening antiretroviral IVR formulations prior to preclinical and clinical evaluation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.