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  • Stimuli-responsive theragrippers for chemomechanical controlled release.

Stimuli-responsive theragrippers for chemomechanical controlled release.

Angewandte Chemie (International ed. in English) (2014-03-19)
Kate Malachowski, Joyce Breger, Hye Rin Kwag, Martha O Wang, John P Fisher, Florin M Selaru, David H Gracias
ABSTRACT

We report on a therapeutic approach using thermo-responsive multi-fingered drug eluting devices. These therapeutic grippers referred to as theragrippers are shaped using photolithographic patterning and are composed of rigid poly(propylene fumarate) segments and stimuli-responsive poly(N-isopropylacrylamide-co-acrylic acid) hinges. They close above 32 °C allowing them to spontaneously grip onto tissue when introduced from a cold state into the body. Due to porosity in the grippers, theragrippers could also be loaded with fluorescent dyes and commercial drugs such as mesalamine and doxorubicin, which eluted from the grippers for up to seven days with first order release kinetics. In an in vitro model, theragrippers enhanced delivery of doxorubicin as compared to a control patch. We also released theragrippers into a live pig and visualized release of dye in the stomach. The design of such tissue gripping drug delivery devices offers an effective strategy for sustained release of drugs with immediate applicability in the gastrointestinal tract.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Calcein-AM, Small Package (20 X 50 μg ), ≥90.0% (HPLC)
Sigma-Aldrich
Doxorubicin hydrochloride, 98.0-102.0% (HPLC)
Sigma-Aldrich
Calcein-AM, suitable for fluorescence, BioReagent, ≥90% (HPLC)
Doxorubicin hydrochloride, European Pharmacopoeia (EP) Reference Standard
USP
Doxorubicin hydrochloride, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Doxorubicin hydrochloride, suitable for fluorescence, 98.0-102.0% (HPLC)
Sigma-Aldrich
Calcein AM solution, 4 mM in DMSO, ≥90% (HPLC), solution