Release of BSA from poly(ortho ester) extruded thin strands

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Developing controlled drug delivery systems is crucial for therapeutic efficacy.
• Poly(ortho esters) offer potential for fabricating protein-releasing implants due to their tunable degradation properties.
• Maintaining protein activity during processing is a significant challenge in biomaterial fabrication.

Purpose of the Study:

• To develop a solventless extrusion method for fabricating poly(ortho ester) implants for protein delivery.
• To investigate the effect of processing parameters on protein release kinetics.
• To identify strategies for eliminating the lag-time in protein release.

Main Methods:

• A solventless extrusion process was employed, mixing powdered polymers with micronized protein.
• Poly(ortho esters) were extruded into 1 mm strands at approximately 70°C.
• In vitro erosion and bovine serum albumin (BSA) release studies were conducted.

Main Results:

• Extrusion of poly(ortho esters) and protein at ~70°C maintained protein activity.
• BSA release and polymer erosion occurred concomitantly after a lag-time, indicating an erosion-controlled release mechanism.
• Addition of 1-5 wt% polyethylene glycol (PEG) or its derivatives, or using a poly(ortho ester)-PEG block copolymer, eliminated the lag-time.

Conclusions:

• Solventless extrusion is a viable method for fabricating protein-releasing poly(ortho ester) implants.
• The release mechanism is primarily erosion-controlled.
• Incorporating PEG or using PEG-containing block copolymers effectively eliminates the lag-time, enabling immediate protein release.