title: Thermoresponsive biodegradable PEG-PCL-PEG based injectable hydrogel for pulsatile insulin delivery.
abstract: An 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, (1) HNMR, 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 1/30(th) 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.
authors.affiliation: Rubber Technology Centre, Indian Institute of Technology, Kharagpur, 721302, India.
authors.forename: Sanal
authors.initials: S
authors.lastname: Payyappilly
authors.forename: Santanu
authors.initials: S
authors.lastname: Dhara
authors.forename: Santanu
authors.initials: S
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002417:Cattle; D002942:Circular Dichroism; D003432:Cross-Linking Reagents / Q000737:chemistry; D004058:Diffusion; D016503:Drug Delivery Systems; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis* / Q000737:chemistry; D007267:Injections; D007328:Insulin / Q000494:pharmacology*; D044367:Phase Transition / Q000187:drug effects; D020442:Poloxamer / Q000138:chemical synthesis / Q000737:chemistry; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D055550:Protein Stability / Q000187:drug effects; D012212:Rheology / Q000187:drug effects; D012996:Solutions; D013696:Temperature; D014783:Viscosity / Q000187:drug effects; D014961:X-Ray Diffraction
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D007328:Insulin; D011091:Polyesters; D012996:Solutions; C502908:poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol); D020442:Poloxamer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols
keywords: biodegradable block copolymer; drug delivery; injectable hydrogel; insulin