miv-150 has been researched along with Papillomavirus-Infections* in 2 studies
2 other study(ies) available for miv-150 and Papillomavirus-Infections
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A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy.
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): MIV-150 (targets HIV-1), zinc acetate (ZA; targets HIV-1 and HSV-2), carrageenan (CG; targets HPV and HSV-2), and levonorgestrel (LNG; 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 28 d (study period) in macaques. The APIs released in vitro and in vivo were active against HIV-1ADA-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. Topics: Administration, Intravaginal; Animals; Antiviral Agents; Carrageenan; Cell Line; Contraceptive Agents, Female; Contraceptive Devices, Female; Drug Delivery Systems; Equipment Design; Female; HeLa Cells; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV Reverse Transcriptase; HIV-1; Human papillomavirus 16; Humans; Levonorgestrel; Macaca mulatta; Papillomavirus Infections; Pregnancy; Pyridines; Urea; Zinc Acetate | 2015 |
A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV.
Prevalent infection with human herpes simplex 2 (HSV-2) or human papillomavirus (HPV) is associated with increased human immunodeficiency virus (HIV) acquisition. Microbicides that target HIV as well as these sexually transmitted infections (STIs) may more effectively limit HIV incidence. Previously, we showed that a microbicide gel (MZC) containing MIV-150, zinc acetate (ZA) and carrageenan (CG) protected macaques against simian-human immunodeficiency virus (SHIV-RT) infection and that a ZC gel protected mice against HSV-2 infection. Here we evaluated a modified MZC gel (containing different buffers, co-solvents, and preservatives suitable for clinical testing) against both vaginal and rectal challenge of animals with SHIV-RT, HSV-2 or HPV. MZC was stable and safe in vitro (cell viability and monolayer integrity) and in vivo (histology). MZC protected macaques against vaginal (p<0.0001) SHIV-RT infection when applied up to 8 hours (h) prior to challenge. When used close to the time of challenge, MZC prevented rectal SHIV-RT infection of macaques similar to the CG control. MZC significantly reduced vaginal (p<0.0001) and anorectal (pā=ā0.0187) infection of mice when 10(6) pfu HSV-2 were applied immediately after vaginal challenge and also when 5Ć10(3) pfu were applied between 8 h before and 4 h after vaginal challenge (p<0.0248). Protection of mice against 8Ć10(6) HPV16 pseudovirus particles (HPV16 PsV) was significant for MZC applied up to 24 h before and 2 h after vaginal challenge (p<0.0001) and also if applied 2 h before or after anorectal challenge (p<0.0006). MZC provides a durable window of protection against vaginal infection with these three viruses and, against HSV-2 and HPV making it an excellent candidate microbicide for clinical use. Topics: Alphapapillomavirus; Anal Canal; Animals; Anti-Infective Agents; Caco-2 Cells; Carrageenan; Female; Gels; HeLa Cells; Herpes Simplex; Herpesvirus 2, Human; Host-Pathogen Interactions; Humans; Macaca mulatta; Mice, Inbred BALB C; Papillomavirus Infections; Pyridines; Rectum; Reverse Transcriptase Inhibitors; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Treatment Outcome; Urea; Vagina; Zinc Acetate | 2014 |