ROS-Sensitive Degradable PEG-PCL-PEG Micellar Thermogel

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Developing degradable polymers is crucial for biomedical applications, especially for disease-responsive systems.
• Polymers with slow hydrolysis kinetics require strategies for accelerated degradation.
• Reactive oxygen species (ROS) are implicated in various diseases, presenting an opportunity for targeted degradation.

Purpose of the Study:

• To synthesize and characterize a novel thermogelling triblock copolymer (PEG-PCL-PEG) sensitive to ROS.
• To evaluate the in vitro and in vivo degradation and gelation properties of the copolymer.
• To assess the potential of the ROS-sensitive thermogel for controlled drug release.

Main Methods:

• Synthesis of poly(ethylene glycol)-polycaprolactone-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymer with an oxalate group.
• Micelle formation and size analysis in aqueous solutions.
• Thermogelling behavior assessment at varying concentrations and temperatures.
• In vitro degradation studies to confirm oxalate group cleavage.
• In vivo gel formation and degradation studies in rat subcutaneous models.
• Drug release studies using cyclosporine A.

Main Results:

• The PEG-PCL-PEG copolymer formed micelles (average size 100 nm) and exhibited thermogelation in a concentration range of 8.0-37.0 wt%.
• Aqueous solutions (25.0-37.0 wt%) formed gels at 37 °C, unlike diblock copolymer solutions.
• In vitro experiments confirmed degradation at the oxalate group, leading to gel dissolution.
• In vivo studies showed complete gel disappearance within 21 days after subcutaneous injection in rats.
• Controlled release of cyclosporine A over 21 days from the in situ formed gel.

Conclusions:

• The developed micelle-based thermogel (PEG-PCL-PEG) is sensitive to ROS and exhibits tunable degradation.
• The material demonstrates successful in situ gel formation and degradation in vivo.
• This ROS-triggering degradable thermogel is a promising injectable biomaterial for drug delivery applications.