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.

A Mucoadhesive Electrospun Nanofibrous Matrix for Rapid Oramucosal Drug Delivery

“…Biaxial extensibility was determined from force-distance profiles generated using a TA.XTplus Texture Analyser (Stable Micro Systems, London, England) fitted with a 2 mm flat cylindrical probe and a 5 kg load cell. The method of testing the extensibility was based on work by Sibeko and coworkers (2009) [34]. The sample was secured onto a ring assembly with a central hole (5 mm diameter), which was attached to a supportive, hollow, raised platform.…”

Poly(vinyl alcohol) nanocomposites based on graphene and graphite oxide: a comparative investigation of property and mechanism

“…[27][28][29][30] For example, graphite oxide (GO) can be well dispersed in water, thus, many interests have been focused on hydrophilic polymers such as poly(vinyl alcohol) (PVA) owing to their hydroxyl groups, which make dispersion easy. As a hydroxyl-rich, water-soluble, biocompatible and non-toxic polymer, PVA is widely used in fuel cells, 31,32 drug delivery, 33,34 functional membranes, 35,36 coating materials, textile sizing and adhesives. 37,38 When graphene/GO is well dispersed in PVA at the molecule level, it brings remarkable enhancements in various properties such as the mechanical properties, thermal stability and electrical conductivity.…”

Crosslinked acetylacetonated poly(vinyl alcohol-co-vinyl acetate) nanocomposites with graphene oxide and reduced graphene oxide: a new way to modify the property of nanocomposites

“…X-Ray diffraction (XRD) patterns were acquired by a PANalytical X'pert diffractometer with Cu-Ka radiation. The scanning rate was 4u min 21 and the range was 5-40u. GO and graphene were analysed as powder and the nanocomposites were analysed as membranes.…”

“…Scanning electron microscopy (TS5136MM) was used to observe the failure surfaces of the nanocomposite films coated with gold. Mechanical properties of neat AcAc-PVA and its nanocomposites were measured using an Instron universal material testing system, and the samples were directly mounted to the sample clamps and stretched at a speed of 10 mm min 21 . In each system, more than five specimens were tested.…”

“…Owing to the excellent biocompatibility and water solubility of poly(vinyl alcohol) (PVA) employed in a variety of biomedical applications such as hydrogels, tissue engineering, drug delivery, membranes, and adhesives, PVA-based composites with various nanofillers have attracted considerable amount of attention in recent years with the aim to obtain high performance materials. [20][21][22][23][24][25][26][27] As compared with carbon nanotubes, 28 nanoclay 29 or other nanofillers, 30 functionalized graphene nanomaterials have its predominance due to the simpler synthesis procedure 31 and efficient improvement in mechanical properties of polymers. 32 Thus, many interests have been focused on PVA-based composites with graphene oxide (GO) and reduced graphene oxide (rGO).…”