Chondroitin/polypyrrole nanocomposite hydrogels for the accurate release of 5‐fluorouracil by electrical stimulation

Abstract

The development of electro‐stimulated drug release devices is an innovative approach to attain the drug delivery in accurate doses at target sites in a programmed manner. In this work, novel electroactive nanocomposite hydrogels were prepared by encapsulating green‐synthesized polypyrrole (PPy) colloids within chondroitin sulfate (CS) networks during the self‐crosslinking of CS via N‐ethyl‐N′‐(3‐dimethylaminopropyl) carbodiimide chemistry. The structural and morphological properties of CS/PPy hydrogels were studied by Fourier‐transformed infrared spectroscopy, scanning electron microscopy, and swelling kinetic measurements. The chemotherapeutic agent 5‐fluorouracil (5‐FU) was loaded into CS/PPy samples by hydrogel swelling method, or alternatively, by pre‐incubating the drug in polymer mixture before crosslinking. Different electrical stimulations can be used to switch ON and accurately tune the 5‐FU delivery from GG/PPy hydrogels. A single pulse potential of 5 V switched on the drug delivery up to 90% from nanocomposite hydrogel, in contrast to the low 5‐FU amount released in a passive form (< 20%). PPy electroactive behavior played a determining role as the main driving force in 5‐FU release activation. Cytotoxicity of hydrogels with and without 5‐FU was examined in normal and cancer cells. Considering the high cytotoxicity of 5‐FU, the ON/OFF 5‐FU release patterns evidenced the potential of CS/PPy hydrogels for electrically controlled drug delivery in implantable or transdermal drug release devices.

Nanocomposite Hydrogels Based on Poly(vinyl alcohol) and Carbon Nanotubes for NIR-Light Triggered Drug Delivery

“…The extract of the H-polymer hydrogel containing 5-FU produced a significant decrease of viability of noncancerous cells (Figure a) and cancer cells (Figure b). Several studies have reported that 5-FU affects the morphology and the cycles of proliferation of both types of cells, inducing apoptosis. , The extract of H-MWCNT-f hydrogel loaded with 5-FU induced a significant decrease of the viability of cancer cells, whereas 93% cell viability was observed for noncancerous cells after 72 h. It is suggested that some interactions between nanotubes and 5-FU resulted in a lower drug availability in the conditioned media exposed to the H-MWCNT-f hydrogel, leading to a higher viability of noncancerous cells (nontoxic dose). This effect was not observed for cancer cells, evidencing a higher sensitivity of these cells to the concentration of 5-FU released from both hydrogels to the conditioned medium.…”

Drug delivery via a 3D electro-swellable conjugated polymer hydrogel

“…Moreover, many diseases affecting high percentages of population require a specific temporal pattern of drug dosing, such as hormonal regulation, pain relief control or chemotherapy (Table ST1, ESI †). However, conventional system do not provide the required specific temporal pattern for the drug dosing, [2][3][4] All these reasons motivate the need for local drug delivery, in a temporally and spatially controlled manner.…”