Characterization & Mathematical Modeling of Silk Based Drug Release Systems.

摘要

Silk fibroin has demonstrated its utility as a natural polymeric biomaterial for the development of polymeric controlled release systems. However, further characterization of relevant release mechanisms and release kinetics of these systems is required in order to fully understand and utilize this material. A methodology towards characterizing the release mechanisms and release kinetics of silk fibroin-based controlled drug release systems is presented. This methodology is accomplished in a four step process of collecting robust in vitro release data, characterizing the appropriate release mechanisms via model fitting, identifying model-parameter-material relationships, and approximating model parameter material relationships with empirical expressions. These empirical expressions are then used to predict model parameters allowing simulation of release. The methodology is demonstrated for two cases, FITC-dextran release from silk films and synthetic dye release from silk films. In both cases a diffusion mechanism is identified as the release mechanism. Binding of synthetic dyes to silk is also assessed and the existence of a more complex desorption-diffusion release mechanism is considered. In most cases binding of the dye to the silk was too weak for desorption to perturb an exclusively diffusional release mechanism.;In addition, a novel continuous flow dissolution apparatus for the collection of in vitro release data was constructed and utilized for the synthetic dye release study. This system allows the collection of data sets while avoiding experimental errors through automation and the increase in the number of observations per release sample based on analysis by real time UV-Vis spectroscopy. This reduction of experimental error and increase in amount of data per sample yields more accurate parameter estimates from mechanistic model fitting. The results from these studies contribute to the characterization of silk as an important alternative biomaterial to current leading polymeric materials for fabricating controlled release devices.