title: Computational molecular modeling and structural rationalization for the design of a drug-loaded PLLA/PVA biopolymeric membrane.
abstract: The purpose of this study was to design, characterize and assess the influence of triethanolamine (TEA) on the physicomechanical properties and release of methotrexate (MTX) from a composite biopolymeric membrane. Conjugated poly(L-lactic acid) (PLLA) and poly(vinyl alcohol) (PVA) membranes were prepared by immersion precipitation with and without the addition of TEA. Drug entrapment efficiency (DEE) and release studies were performed in phosphate buffered saline (pH 7.4, 37 degrees C). Scanning electron microscopy elucidated the membrane surface morphology. Computational and structural molecular modeling rationalized the potential mechanisms of membrane formation and MTX release. Bi-axial force-distance (F-D) extensibility profiles were generated to determine the membrane toughness, elasticity and fracturability. Membranes were significantly toughened by the addition of TEA as a discrete rubbery phase within the co-polymer matrix. MTX-TEA-PLLA-PVA membranes were tougher (F = 89 N) and more extensible (D = 8.79 mm) compared to MTX-PLLA-PVA (F = 35 N, D = 3.7 mm) membranes as a greater force of extension and fracture distance were required (N = 10). DEE values were relatively high (>80%, N = 5) for both formulations. Photomicrographs revealed distinct crystalline layered morphologies with macro-pores. MTX was released by tri-phasic kinetics with a lower fractional release of MTX from MTX-TEA-PLLA-PVA membranes compared to MTX-PLLA-PVA. TEA provided a synergistic approach to improving the membrane physicomechanical properties and modulation of MTX release. The composite biopolymeric membrane may therefore be suitable for the novel delivery of MTX in the treatment of chronic primary central nervous system lymphoma.
authors.affiliation: Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa.
authors.forename: B
authors.initials: B
authors.lastname: Sibeko
authors.forename: V
authors.initials: V
authors.lastname: Pillay
authors.forename: Y E
authors.initials: YE
authors.lastname: Choonara
authors.forename: R A
authors.initials: RA
authors.lastname: Khan
authors.forename: G
authors.initials: G
authors.lastname: Modi
authors.forename: S E
authors.initials: SE
authors.lastname: Iyuke
authors.forename: D
authors.initials: D
authors.lastname: Naidoo
authors.forename: M P
authors.initials: MP
authors.lastname: Danckwerts
mesh_terms: D000327:Adsorption; D003198:Computer Simulation; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D055119:Elastic Modulus; D004983:Ethanolamines / Q000737:chemistry*; D006244:Hardness; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D008567:Membranes, Artificial; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D016062:Porosity; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D004983:Ethanolamines; D008567:Membranes, Artificial; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D011142:Polyvinyl Alcohol; C009546:triethanolamine