Title: Combinatorial Synthesis
of and Drug Delivery from Biodegradable Polyanhydrides
Speaker: Prof. Balaji
Narsimhan, CBE, ISU
Abstract:
We have demonstrated that polycondensation reactions can be carried out
in a combinatorial fashion and
that the polymer library can be screened at high throughput using a
rapid prototyping technique to fabricate
multiwell substrates. A linearly varying compositional library of 100
different biodegradable polyanhydride
random copolymers that are promising carriers for controlled drug
delivery was designed, fabricated, and
characterized by IR microscopy within a few hours. The polyanhydride
copolymer library was based on
1,6-bis(p-carboxyphenoxy)hexane (CPH) and sebacic anhydride (SA) and
was characterized with infrared
microspectroscopy to determine the composition within each well. Since
degradation and release rates depend
on copolymer composition, we also developed new high-throughput methods
to investigate drug release
from this library of copolymers by designing specific wells for each
task. A subset of this library was
chosen, and a substrate was designed and fabricated to enable the
synthesis and monitoring of dye dissolution
from a range of polyanhydride copolymers in a parallel fashion using a
CCD camera. Multisample substrates
were fabricated with a novel rapid prototyping method that consists of
an organic solvent-resistant array of
10 X 10 microwells. The libraries were deposited with a
custom-built liquid dispensing
system consisting of a series of computer-controlled volume-dispensing
pumps and XYZ motion stages. The
parallel dye dissolution study displayed a decreasing rate of release
with increasing CPH content. This
result agrees with previously published data for dye release from
poly(CPH-co-SA) copolymers. The
methodology described in this work is amenable to numerous applications
in the arenas of high-throughput
polymer synthesis and characterization.