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.

Thermosensitive block copolymer hydrogels based on poly(ɛ‐caprolactone) and polyethylene glycol for biomedical applications: State of the art and future perspectives

“…Therefore, differently from PEG/PCL multiblock hydrogels, gelling mechanism of concentrated solutions of triblock PEG/PCL copolymers may be influenced by crystallization, due to their relatively fast crystallization rate compared to multiblock copolymers. Similarly, Payyappilly et al showed that PECE hydrogels (30 % concentration) partially crystallized, showing a melting peak at around 39°C [Fig. (c)].…”

“…Rheological characterization is also helpful to measure the molecular weight of hydrogel chains between the crosslinks ( M c ), according to the following equation: where G ′ is the elastic modulus of the linear region of the modulus versus stress sweep plot, ρ is the polymer density, R is molar gas constant, and T is the test temperature. M c decreases with increasing polymer concentration in hydrogel, affecting hydrogel permeability to molecules.…”

Phenylboronic Acid Appended Pyrene‐Based Low‐Molecular‐Weight Injectable Hydrogel: Glucose‐Stimulated Insulin Release

“…Hydrogels are finding significant promise as drug delivery vehicle 40. 41 The interstitial space within the fibrillar network of the hydrogel might help in the entrapment of a drug and release it at a rate, which is dependent on the porosity of the hydrogel correlated to the extent of the crosslinked SAFIN 40. 41 Hence, drug diffusion is supposed to be tuned by the degree of swelling of the hydrogel.…”

“…41 The interstitial space within the fibrillar network of the hydrogel might help in the entrapment of a drug and release it at a rate, which is dependent on the porosity of the hydrogel correlated to the extent of the crosslinked SAFIN 40. 41 Hence, drug diffusion is supposed to be tuned by the degree of swelling of the hydrogel. To this end, glucose‐stimulated swelling of the LMHG 1 a (as observed from our SEM study), encouraged us to explore its possible application for in vitro drug release through a diffusion pathway 40.…”

Pain Management Via Local Anesthetics and Responsive Hydrogels

“…However, the nondegradability and poor in vivo stability of the Pluronics are considered limitations for clinical applications [53]. Recent effort has therefore, been focused on developing biodegradable PEG-based injectable hydrogels with degradable hydrophobic blocks such as poly(ε-caprolactone), polyesters and polyurethanes [54–56]. …”