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Abstract Implantable, bioresorbable drug delivery systems offer an alternative to current drug administration techniques; allowing for patient‐tailored drug dosage, while also increasing patient compliance. Mechanistic mathematical modeling allows for the acceleration of the design of the release systems, and for prediction of physical anomalies that are not intuitive and may otherwise elude discovery. This study investigates short‐term drug release as a function of water‐mediated polymer phase inversion into a solid depot within hours to days, as well as long‐term hydrolysis‐mediated degradation and erosion of the implant over the next few weeks. Finite difference methods are used to model spatial and temporal changes in polymer phase inversion, solidification, and hydrolysis. Modeling reveals the impact of non‐uniform drug distribution, production and transport of H+ions, and localized polymer degradation on the diffusion of water, drug, and hydrolyzed polymer byproducts. Compared to experimental data, the computational model accurately predicts the drug release during the solidification of implants over days and drug release profiles over weeks from microspheres and implants. This work offers new insight into the impact of various parameters on drug release profiles, and is a new tool to accelerate the design process for release systems to meet a patient specific clinical need.
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This content will become publicly available on June 12, 2026
Effect of Mechanical Loading on PLGA Biodegradation
Poly(lactic-co-glycolic) acid (PLGA) has been widely implemented in tissue engineering and drug delivery systems, stemming from its biocompatibility, controllable biodegradation, non-toxicity, non-immunogenicity, and tunable mechanical properties. PLGA exhibits a broad range of degradation times and modes, which can be finely tuned by adjusting various parameters, namely by altering the ratio of lactide and glycolide units, molecular weight, end group functionality, specimen geometry, processing temperature, and chemistry of the surrounding medium. To tailor the degradation profile, the in vitro profile should closely reflect the in vivo profile; however, the effects of mechanical loading coupled with hydrolysis on PLGA biodegradation are typically overlooked. To this end, this study investigates the combined effects of mechanical loading and hydrolysis at 37ºC on the changes in the chemical and physical properties of PLGA as it degrades with time. We found that after several days of combined loading and hydrolysis at 37ºC PLGA significantly creeps, whereas non-loaded (but hydrolyzed) specimens only slightly elongated after relatively long-term hydrolysis (~60 days). Despite this observation and perhaps counterintuitively, the hydrolyzed non-loaded samples exhibited faster degradation than hydrolyzed loaded samples. Additionally, our studies indicated the presence of bulk erosion in hydrolyzed non-loaded samples and surface erosion in hydrolyzed loaded samples. We also observed (only) physical ageing in control samples (loaded and non-loaded samples that were not immersed in PBS but exposed to 37 °C). Based on these observations, we discuss potential underlying mechanisms for the observed differences in the biodegradation behavior of PLGA specimens with and without mechanical loading.
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- Award ID(s):
- 2013696
- PAR ID:
- 10649029
- Publisher / Repository:
- Polymer Degradation and Stability
- Date Published:
- Journal Name:
- Polymer degradation and stability
- ISSN:
- 0141-3910
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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