Characterization & Mathematical Modeling of Silk Based Drug Release Systems.
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 ... read morekinetics 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
Thesis (Ph.D.)--Tufts University, 2012.
Submitted to the Dept. of Chemical and Biological Engineering.
Advisor: David Kaplan.
Committee: Kyongbum Lee, Anthony Barry, and Bruce Paniliatis.
Keywords: Chemical engineering, Biomedical engineering, and Pharmaceutical sciences.read less