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

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Developing injectable hydrogels for controlled drug release is crucial for therapeutic applications.
• Temperature-responsive materials offer unique possibilities for triggered release mechanisms.
• Biodegradable polymers are desirable for minimizing long-term effects in vivo.

Purpose of the Study:

• To prepare and characterize an injectable, biodegradable, temperature-responsive hydrogel based on a triblock copolymer (PEG-PCL-PEG, PECE).
• To investigate the potential of the PECE hydrogel for pulsatile, temperature-controlled release of insulin.
• To compare the properties and performance of the PECE hydrogel with a non-biodegradable hydrogel (Pluronic).

Main Methods:

• Synthesis of poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) triblock copolymer via ring-opening bulk copolymerization.
• Characterization of the copolymer using FT-IR, 1HNMR, and gel permeation chromatography.
• Evaluation of temperature-responsive sol-gel transition, crystallinity, in vitro insulin release kinetics, and insulin secondary structure post-release.

Main Results:

• The synthesized PECE copolymer formed an injectable hydrogel that transitioned from solution at room temperature to gel at 37°C.
• In vitro insulin release from PECE hydrogels showed a Fickian diffusion profile, similar to Pluronic, with significantly lower viscosity.
• A threefold increase in the Fickian diffusion coefficient was observed between 34°C and 40°C due to PCL crystalline melting, enabling pulsatile insulin release correlated with temperature changes.

Conclusions:

• The injectable biodegradable PECE hydrogel demonstrates effective temperature-responsive, pulsatile insulin release.
• PECE hydrogels offer a tunable platform for controlled drug delivery with potential advantages over existing non-biodegradable systems.
• The temperature-induced modulation of diffusion kinetics highlights the potential for precise control over drug release profiles.