Optimization of a polymer composite employing molecular mechanic simulations and artificial neural networks for a novel intravaginal bioadhesive drug delivery device

Abstract

This study aimed at elucidating an optimal synergistic polymer composite for achieving a desirable molecular bioadhesivity and Matrix Erosion of a bioactive-loaded Intravaginal Bioadhesive Polymeric Device (IBPD) employing Molecular Mechanic Simulations and Artificial Neural Networks (ANN). Fifteen lead caplet-shaped devices were formulated by direct compression with the model bioactives zidovudine and polystyrene sulfonate. The Matrix Erosion was analyzed in simulated vaginal fluid to assess the critical integrity. Blueprinting the molecular mechanics of bioadhesion between vaginal epithelial glycoprotein (EGP), mucin (MUC) and the IBPD were performed on HyperChem 8.0.8 software (MM+ and AMBER force fields) for the quantification and characterization of correlative molecular interactions during molecular bioadhesion. Results proved that the IBPD bioadhesivity was pivoted on the conformation, orientation, and poly(acrylic acid) (PAA) composition that interacted with EGP and MUC present on the vaginal epithelium due to heterogeneous surface residue distributions (free energy= −46.33 kcalmol⁻¹). ANN sensitivity testing as a connectionist model enabled strategic polymer selection for developing an IBPD with an optimally prolonged Matrix Erosion and superior molecular bioadhesivity (ME = 1.21-7.68%; BHN = 2.687-4.981 N/mm²). Molecular modeling aptly supported the EGP-MUC-PAA molecular interaction at the vaginal epithelium confirming the role of PAA in bioadhesion of the IBPD once inserted into the posterior fornix of the vagina.

Keywords::

• Artificial neural networks
• molecular mechanic simulations
• sensitivity testing
• matrix erosion
• molecular bioadhesivity
• optimization
• intravaginal drug delivery device

Acknowledgements

St. John’s University of Tanzania is sincerely acknowledged.

Declaration of interest

This research is supported by the Norwegian Agency for Development Co-operation (NORAD)-NORWAY, and by grants from the National Research Foundation (NRF) of South Africa and the Faculty Research Committee, University of Witwatersrand, Johannesburg, South Africa. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.