Stimuli‐Responsive Theragrippers for Chemomechanical Controlled Release

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.

Spatiotemporal Modification of Stimuli-Responsive Hyaluronic Acid/Poly(N-isopropylacrylamide) Hydrogels

“…25,32,33,34,35 Applications of thermally responsive PNIPAM-based hydrogels vary from temperature-responsive cell culture dishes to microlenses and bioactuators. 36,37,38,39,40,41,42,43,44,45 Some PNIPAM-based materials have thermally induced the release of proteins and several therapeutics such as heparin, ovalbumin, doxorubicin, mesalamine, and other model compounds. 40,46,47,48,49,50 Self-propelling microjets made of 2D PNIPAM hydrogels have been studied to mimic the movement of biological swimmers triggered by changing temperature.…”

“…36,37,38,39,40,41,42,43,44,45 Some PNIPAM-based materials have thermally induced the release of proteins and several therapeutics such as heparin, ovalbumin, doxorubicin, mesalamine, and other model compounds. 40,46,47,48,49,50 Self-propelling microjets made of 2D PNIPAM hydrogels have been studied to mimic the movement of biological swimmers triggered by changing temperature. 42 Furthermore, patterned and functionalized PNIPAM 2D hydrogels have been used to fabricate cell culture dishes with dual cell adhesion properties.…”

High‐Resolution SPECT Imaging of Stimuli‐Responsive Soft Microrobots

“…These gels can be remotely controlled using magnetic fields to reach a target location, or to induce a shape transition. These morphological changes are used to modulate their dynamic behavior or to release therapeutic agents …”

MEMS: Enabled Drug Delivery Systems

“…Temperature responsive hydrogels where used to construct grippers composed of poly( N -isopropylacrylamide-co-acrylic acid) and poly(propylene fumarate) for sustained drug release in the gastrointestinal tract. [ 36 ] Drug release from the grippers into the tissue occurred at body temperatures above 32 °C.…”