In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization
Drug Development and Industrial Pharmacy
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Fac. of Hlth. Sci., Sch. of Therapeut. Sci., University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, South Africa; Department of Pharmaceutics and Formulation Sciences, School of Pharmacy and Pharmaceutical Sciences, St. John's University of Tanzania, Dodoma, Tanzania; Department of Paraclinical Science, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria, South Africa
Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery. Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings. Results and discussion: There was a big deviation between the Tg of the polymeric caplet from the Tg's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012-0.332 mg/mL and 0.009-0.256 mg/mL for AZT and PSS over 1-28 d. Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents. © 2014 Informa Healthcare USA, Inc. All rights reserved.
anti human immunodeficiency virus agent; ethyl cellulose; polyacrylic acid; polyamide; polylactide; polystyrenesulfonic acid; polyvinyl alcohol; zidovudine; animal experiment; Article; compression; controlled drug release; controlled study; differential scanning calorimetry; drug delivery system; female; histopathology; Human immunodeficiency virus 1; in vitro study; in vivo study; infrared spectrometry; infrared spectroscopy; molecular mechanics; mucoadhesive polymeric caplet; nonhuman; polymerization; scanning electron microscope; simulation; tablet; temperature modulated differential scanning calorimetry; thermal analysis