A Repertoire of Peptide Tags for Controlled Drug Release
from Injectable Noncovalent Hydrogel
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Abstract
A repertoire of conjugable tags for
controlling the release of
drugs from biomaterials is highly interesting for the development
of combinatorial drug administration techniques. This paper describes
such a system of 11 peptide tags derived from our previous work on
a physical hydrogel system cross-linked through peptide–heparin
interactions. The release kinetics of the tags correlate well with
their affinity to heparin and obey Fick’s second law of diffusion,
with the exception of the ATIII peptide, which displays a stable release
profile close to a zero-order reaction. A system for release experiments
over seven months was built, using the hydrogel matrix as a barrier
between the reservoirs of tagged compounds and supernatant. The gel
matrix can be injected without affecting the releasing properties.
A tagged cyclosporin A derivative was also tested, and its release
was monitored by measuring its biological activity. This work represents
a design of biomaterials with an integral system of drug delivery,
where both the assembly process of the matrix and affinity capture/release
of tagged compounds are based on the noncovalent interaction of heparin
with one class of peptides