In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

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 T_g of the polymeric caplet from the T_g'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.