Development and characterization of poly(vinylidene fluoride)-poly(acrylic acid) pore-filled pH -sensitive membranes and potential application on controlled drug release for ruminant animals.

摘要

A new pore-filled pH-sensitive membrane was developed by in situ cross-linking poly(acrylic acid) (PAA) inside poly(vinylidene fluoride) (PVDF) hydrophobic microporous substrate. The developed membranes demonstrated a rapid and reversible response of flux to environmental pH as the pH changed from acidic to neutral.;The membrane pore structure (pore radius and pore density), at both pH acidic and neutral, was investigated intensively. The results of this study, for the first time, quantitatively demonstrate the pore structure variation, as a function of environmental pH, for the PAA pore-filled membranes in PVDF substrate.;The pore radius at pH acidic was calculated by the pore-filled model. The pore radius at pH neutral was estimated by means of three methods: fitting the extended Nernst-Plank equation (ENPE); fitting the Spiegler-Kedem model (SK) combined with the steric-hindrance pore model (SHP); and the calculation of the gel correlation length. The pore radii estimated by ENPE and by SK and SHP were close to each other and comparable with the results calculated from the PAA gel correlation length. From the pore radii, at both pH acidic and neutral, the pore densities were calculated. The effects of the gel volume fraction and the cross-linking degree on the pore sizes and the pore densities at both pH acidic and neutral were investigated.;The potential application of the developed membranes on controlled drug release in ruminant animals was explored by studying the membrane performance for a model drug, salicylic acid, in both a pressure-driven system and a diffusion dialysis system. This is the first time that the application of pore-filled pH-sensitive membranes is investigated on the controlled drug release for ruminant animals. The results of this work advance the understanding and description of the membrane in pharmaceutical delivery system for use in ruminant animals.;By investigating the membrane flux as a function of environmental pH, the understanding of the effects of mass gain (or gel volume fraction) and the cross-linking degree on the performance of the pore-filled pH-sensitive membranes is advanced.;The membrane permeability for salicylic acid was determined by linear regression of the diffusion dialysis experiment data. The permeability at pH neutral was much lower than that at pH acidic due to the Donnan exclusion effect. The permeabilities at both pH acidic and neutral decreased as the mass gain increasing due to the influence of the membrane porosity and tortuosity, the partition coefficient, and the drug diffusion coefficient. As the mass gain increased, the ratio of the membrane permeability at pH acidic to that at pH neutral became greater.