A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy
| Autor: | Meropi Aravantinou, Jessica Kenney, James Blanchard, José A. Fernández-Romero, Jolanta Wilk, Larisa Kizima, Samantha Seidor, Kevin Roberts, Melissa Robbiani, Narender Kumar, Keith Levendosky, Brooke Grasperge, Asa Wesenberg, Olga Mizenina, Thomas M. Zydowsky, Shweta R. Ugaonkar, Shimin Zhang, Agegnehu Gettie, Nina Derby, Aixa Rodriguez |
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| Jazyk: | angličtina |
| Předmět: |
Efficacy
Pyridines Herpesvirus 2 Human Zinc Acetate Human immunodeficiency virus (HIV) Pharmaceutical Science HIV Infections Levonorgestrel Pharmacology Carrageenan medicine.disease_cause Antiviral Agents Cell Line Drug Delivery Systems Pregnancy In vivo Microbicide Contraceptive Agents Female Animals Humans Urea Medicine Active ingredient Human papillomavirus 16 Herpes Genitalis business.industry Papillomavirus Infections Contraceptive Devices Female Equipment Design Core–matrix design Macaca mulatta Vaginal ring Multipurpose prevention technology HIV Reverse Transcriptase 3. Good health Microbicides Microbicides for sexually transmitted diseases Administration Intravaginal Intravaginal ring Contraception HIV-1 Female business Unintended pregnancy HeLa Cells medicine.drug |
| Zdroj: | Journal of Controlled Release. :57-68 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2015.06.018 |
| Popis: | Women urgently need a self-initiated, multipurpose prevention technology (MPT) that simultaneously reduces their risk of acquiring HIV-1, HSV-2, and HPV (latter two associated with increased risk of HIV-1 acquisition) and prevents unintended pregnancy. Here, we describe a novel core–matrix intravaginal ring (IVR), the MZCL IVR, which effectively delivered the MZC combination microbicide and a contraceptive. The MZCL IVR contains four active pharmaceutical ingredients (APIs): M IV-150 (targets HIV-1), zinc acetate ( Z A; targets HIV-1 and HSV-2), carrageenan ( C G; targets HPV and HSV-2), and levonorgestrel ( L NG; targets unintended pregnancy). The elastomeric IVR body (matrix) was produced by hot melt extrusion of the non-water swellable elastomer, ethylene vinyl acetate (EVA-28), containing the hydrophobic small molecules, MIV-150 and LNG. The solid hydrophilic core, embedded within the IVR by compression, contained the small molecule ZA and the macromolecule CG. Hydrated ZA/CG from the core was released by diffusion via a pore on the IVR while the MIV-150/LNG diffused from the matrix continuously for 94 days (d) in vitro and up to 28d (study period) in macaques. The APIs released in vitro and in vivo were active against HIV-1 ADA-M , HSV-2, and HPV16 PsV in cell-based assays. Serum LNG was at levels associated with local contraceptive effects. The results demonstrate proof-of-concept of a novel core–matrix IVR for sustained and simultaneous delivery of diverse molecules for the prevention of HIV, HSV-2 and HPV acquisition, as well as unintended pregnancy. |
| Databáze: | OpenAIRE |
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