Engineering microenvironment of biodegradable polyester systems for drug stability and release control

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) are extensively utilized for sustained drug delivery due to their biocompatibility and biodegradability.
• These polymers are approved by the US FDA and have a proven track record in pharmaceutical applications.
• Emerging drug delivery applications necessitate a deeper understanding of the microenvironment changes during polymer degradation.

Purpose of the Study:

• To review the challenges associated with the acidifying microenvironment of degrading PLA and PLGA systems.
• To discuss the impact of this acidic microenvironment on drug stability and release kinetics.
• To explore strategies for mitigating the detrimental effects of polymer degradation on drug delivery performance.

Main Methods:

• Literature review of studies on PLA and PLGA degradation.
• Analysis of the chemical changes within the polymer microenvironment during degradation.
• Examination of the effects of pH changes on the stability and release profiles of various drugs.
• Identification and categorization of methods to control or neutralize acidic byproducts.

Main Results:

• Acidic byproduct generation during PLA and PLGA degradation can significantly compromise drug stability.
• Altered microenvironment pH affects the release kinetics, often leading to premature or inconsistent drug release.
• Various strategies, including buffering agents and polymer modification, can mitigate these adverse effects.
• Successful mitigation strategies preserve drug integrity and ensure predictable release profiles.

Conclusions:

• The acidifying microenvironment of degrading PLA and PLGA poses a significant challenge for long-term drug delivery.
• Understanding and controlling the microenvironmental pH is crucial for optimizing drug stability and achieving desired release kinetics.
• Implementing strategies to manage polymer degradation byproducts is essential for the successful development of advanced drug delivery systems.