Biodegradable triblock copolymer microspheres based on thermosensitive sol-gel transition

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Chemistry

Background:

• Sustained protein delivery is crucial for managing chronic diseases like diabetes.
• Conventional microsphere preparation often involves organic solvents, posing safety and environmental concerns.
• Biodegradable tri-block copolymers offer potential for controlled release applications.

Purpose of the Study:

• To design and evaluate thermosensitive, biodegradable PLGA-PEG-PLGA microspheres for sustained protein delivery.
• To achieve solvent-free microsphere preparation using an aqueous-based method.
• To compare the performance of these novel microspheres (Msp A) with conventionally prepared ones (Msp B).

Main Methods:

• Microspheres (Msp A) were prepared using an aqueous-based sol-gel method, avoiding organic solvents.
• Microspheres (Msp B) were prepared using the conventional water-in-oil-in-water double emulsion method with methylene chloride.
• Insulin loading, release kinetics (HPLC, CD spectroscopy), structural integrity, and in vivo efficacy in diabetic rats were assessed.

Main Results:

• Msp A exhibited significantly reduced initial burst release and continuous insulin release (>85%) over 3 weeks.
• Insulin released from Msp A retained its secondary structural integrity, unlike Msp B.
• In vivo studies in diabetic rats showed Msp A provided sustained insulin release and blood glucose control for at least 10 days, avoiding the hypoglycemia seen with Msp B.

Conclusions:

• Solvent-free PLGA-PEG-PLGA microspheres (Msp A) offer a promising platform for sustained, safe, and effective protein delivery.
• The aqueous-based method preserves protein integrity and improves release profiles compared to conventional solvent-based methods.
• This approach represents a significant advancement in developing biodegradable drug delivery systems.