In vivo evaluation of the release of zidovudine and polystyrene sulfonate from a dual intravaginal bioadhesive polymeric device in the pig model
Journal of Pharmaceutical Sciences
Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown 2193, Johannesburg, South Africa; Central Animal Services, University of the Witwatersrand, 7 York Road, Parktown 2193, Johannesburg, South Africa; Chris Hani Baragwanath Hospital, Department of Gynaecology and Obstetrics, Bertsham 2013, Johannesburg, South Africa; Manav Rachna International University, Aravali Hills, Faridabad, India
This study focused on determining the concentration of zidovudine (AZT) and polystyrene sulfonate (PSS) in the plasma and vaginal tissue of the large white pig from an intravaginal bioadhesive polymeric device (IBPD). Biocompatible polymers were compressed with AZT and PSS into caplet-shaped devices for insertion into the posterior fornix of the pig vagina. A total of 25 pigs were used in this study. Plasma was sampled from the jugular vein at various time points after insertion of the IBPD reaching 28 days. At day 28, the pigs were euthanized and vaginal tissue was removed and digested with subtilisin for AZT and PSS extraction. The mean concentration detected in vaginal tissue at day 28 was 1.214 ± 0.062 mg/mL for AZT and 1.400 ± 0.071 mg/mL for PSS. Plasma concentration was significantly lower for AZT (0.332 ± 0.014 mg/mL) and PSS (0.256 ± 0.013 mg/mL). This indicated higher retention of AZT and PSS within the vaginal tissue. Molecular mechanics simulations blueprinted polymer-drug-mucin force-field interactions and energies that explicated the spatial preference of AZT and PSS for the vaginal tissue. Histopathotoxicity studies revealed negative-to-mild foreign body events and results strongly suggest that the IBPD may be suitable for prolonged intravaginal drug delivery in preventing the transmission of sexually transmitted infections and HIV/AIDS. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association.
mucin; polymer; polystyrenesulfonic acid; subtilisin; zidovudine; anti human immunodeficiency virus agent; biomaterial; chelating agent; polystyrene derivative; polystyrenesulfonic acid; zidovudine; acquired immune deficiency syndrome; animal experiment; animal tissue; article; biocompatibility; brain fornix; controlled study; device; drug blood level; drug delivery system; drug isolation; drug release; drug tissue level; energy; epithelium hyperplasia; female; foreign body; Human immunodeficiency virus infection; in vivo study; intravaginal bioadhesive polymeric device; jugular vein; molecular mechanics; nonhuman; sexually transmitted disease; simulation; vagina; adhesion; animal; blood; chemistry; devices; drug delivery system; intravaginal drug administration; metabolism; swine; Adhesiveness; Administration, Intravaginal; Animals; Anti-HIV Agents; Biocompatible Materials; Chelating Agents; Drug Delivery Systems; Female; Polymers; Polystyrenes; Swine; Vagina; Zidovudine