title: 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/mm(2)). 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.
authors.affiliation: University of the Witwatersrand, Department of Pharmacy and Pharmacology, 7 York Road, Parktown, 2193, Johannesburg, South Africa.
authors.forename: Valence M K
authors.initials: VM
authors.lastname: Ndesendo
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Eckhart
authors.initials: E
authors.lastname: Buchmann
authors.forename: Leith C R
authors.initials: LC
authors.lastname: Meyer
authors.forename: Riaz A
authors.initials: RA
authors.lastname: Khan
mesh_terms: D000268:Adhesiveness; D000269:Adhesives / Q000737:chemistry* / Q000378:metabolism; D000282:Administration, Intravaginal; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000954:Antigens, Surface / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016571:Neural Networks, Computer; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D014621:Vagina / Q000378:metabolism; D015215:Zidovudine / Q000008:administration & dosage*
chemical_list: D000269:Adhesives; D019380:Anti-HIV Agents; D000954:Antigens, Surface; D006023:Glycoproteins; D011108:Polymers; D015215:Zidovudine