In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization |
| |
Authors: | Valence M. K. Ndesendo Yahya E. Choonara Leith C. R. Meyer Pradeep Kumar Lomas K. Tomar Charu Tyagi |
| |
Affiliation: | 1. Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutic Sciences, University of the Witwatersrand, Johannesburg, Parktown, South Africa,;2. Department of Pharmaceutics and Formulation Sciences, School of Pharmacy and Pharmaceutical Sciences, St. John's University of Tanzania, Dodoma, Tanzania, and;3. Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutic Sciences, University of the Witwatersrand, Johannesburg, Parktown, South Africa,;4. Department of Paraclinical Science, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria, South Africa |
| |
Abstract: | 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. |
| |
Keywords: | Histopathological studies mucoadhesive polymeric caplet polymeric-controlled drug release temperature-modulated differential scanning calorimetry |
|
|