Regulating drug release from pH- and temperature-responsive electrospun CTS-g-PNIPAAm/poly(ethylene oxide) hydrogel nanofibers

Abstract

Temperature- and pH-responsive polymers have been widely investigated as smart drug release systems. However, dual-sensitive polymers in the form of nanofibers, which is advantageous in achieving rapid transfer of stimulus to the smart polymeric structures for regulating drug release behavior, have rarely been explored. In this study, chitosan-graft-poly(N-isopropylacrylamide) (CTS-g-PNIPAAm) copolymer was synthesized by using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxy succinimide (NHS) as grafting agents to graft carboxyl-terminated PNIPAAm (PNIPAAm-COOH) chains onto the CTS biomacromolecules, and then CTS-g-PNIPAAm with or without bovine serum albumin (BSA) was fabricated into nanofibers through electrospinning using poly(ethylene oxide) (PEO, 10 wt%) as a fiber-forming facilitating additive. The BSA laden CTS-g-PNIPAAm/PEO hydrogel nanofibers were tested to determine their drug release profiles by varying pH and temperature. Finally, cytotoxicity of the CTS-g-PNIPAAm/PEO hydrogel nanofibers was evaluated by assaying the L929 cell proliferation using the MTT method. It was found that the synthesized CTS-g-PNIPAAm possessed a temperature-induced phase transition and lower critical solution temperature (LCST) at 32° C in aqueous solutions. The rate of BSA release could be well modulated by altering the environmental pH and temperature of the hydrogel nanofibers. The CTS-g-PNIPAAm/PEO hydrogel nanofibers supported L929 cell growth, indicative of appropriate cytocompatibility. Our current work could pave the way towards developing multi-stimuli responsive nanofibrous smart materials for potential applications in the fields of drug delivery and tissue engineering.