Thermoresponsive biodegradable PEG‐PCL‐PEG based injectable hydrogel for pulsatile insulin delivery

AbstractAn injectable biodegradable hydrogel was prepared for temperature‐responsive pulsatile release of insulin. Triblock copolymer of poly(ethylene glycol)‐poly(ε‐caprolactone)‐poly(ethylene glycol) (PEG‐PCL‐PEG, PECE) was prepared by ring opening bulk copolymerization and characterized using FT‐IR, 1HNMR, and gel permeation chromatography. Aqueous solution of PECE formed an injectable hydrogel, which was solution at room temperature and transformed into gel at 37°C. The temperature‐responsive sol–gel transition and crystallinity of PECE hydrogel was studied and compared with pluronic, a well‐studied nonbiodegradable injectable hydrogel. In vitro release study revealed that insulin release profile of PECE was similar to pluronic, and its viscosity was 1/30th of pluronic sol at 10,000 s−1 shear rate. Release behavior of insulin from PECE hydrogels followed Fickian diffusion of first order. Insulin retained its secondary structure after release as confirmed by circular dichroism spectrum. A threefold increase in Fickian diffusion coefficient was evidenced when temperature was increased from 34 to 40°C because of crystalline melting of PCL part of PECE. Pulsatile release of insulin showed a correlation coefficient of 0.90 with the change of temperature. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1500–1509, 2014.