Often neglected: PLGA/PLA swelling orchestrates drug release: HME implants.

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery

Background:

• Controlled drug release systems are vital for therapeutic efficacy.
• Poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA) are widely used biodegradable polymers for implants.
• Understanding the release mechanisms of drugs from these implants is crucial for optimizing their design.

Purpose of the Study:

• To investigate the role of polymer swelling in the controlled release of dexamethasone from PLGA and PLA implants prepared by hot melt extrusion.
• To characterize the influence of lactic acid:glycolic acid ratio and drug loading on the release profile.
• To elucidate the mass transport phenomena governing drug release.

Main Methods:

• Preparation of PLGA and PLA implants with varying compositions using hot melt extrusion (HME).
• Characterization of implants before and after incubation in phosphate buffer (pH 7.4, 37°C).
• Analysis of polymer swelling, molecular weight changes, and dexamethasone release kinetics.

Main Results:

• Polymer swelling was identified as the key factor orchestrating dexamethasone release, with a significant lag time observed.
• Initial limited water penetration hindered drug dissolution and diffusion.
• Hydrolysis of polyesters increased hydrophilicity and triggered substantial swelling (600-1700%), enabling significant drug release.
• No burst release was observed from the initially non-porous implants.

Conclusions:

• Polymer swelling plays a critical role in enabling controlled dexamethasone release from PLGA and PLA implants.
• The observed release mechanism is governed by a transition from limited water uptake to significant swelling, driven by polymer degradation.
• This study provides valuable insights into the design of biodegradable implants for sustained drug delivery.