Abstract
This study analyzes the swelling behavior of native, unmodified, spherically uniform, monodisperse poly(lactic-co-glycolic acid) (PLGA) microparticles in a robust high-throughput manner. This work contributes to the complex narrative of PLGA microparticle behavior and release mechanisms by complementing and extending previously reported studies on intraparticle microenvironment, degradation, and drug release. Microfluidically produced microparticles are incubated under physiological conditions and observed for 50 days to generate a profile of swelling behavior. Microparticles substantially increase in size after 15 days, continue increasing for 30 days achieving size dependent swelling indices between 49 and 83%. Swelling capacity is found to correlate with pH. Our study addresses questions such as onset, duration, swelling index, size dependency, reproducibility, and causal mechanistic forces surrounding swelling. Importantly, this study can serve as the basis for predictive modeling of microparticle behavior and swelling capacity, in addition to providing clues as to the microenvironmental conditions that encapsulated material may experience.
Highlights
This study analyzes the swelling behavior of native, unmodified, spherically uniform, monodisperse poly(lactic-co-glycolic acid) (PLGA) microparticles in a robust high-throughput manner
In order for PLGA microparticles to be efficient drug delivery devices, it is critical to understand the physiochemical properties of PLGA as they help in the prediction and modification of polymer performance as it relates to drug stability and subsequent release
The dispersed phase consisted of PLGA dissolved in the non-toxic organic solvent, dimethyl carbonate (DMC)
Summary
This study analyzes the swelling behavior of native, unmodified, spherically uniform, monodisperse poly(lactic-co-glycolic acid) (PLGA) microparticles in a robust high-throughput manner. Disk, or microparticle form, PLGA is said to have size dependent autocatalytic capabilities in which the center of a PLGA matrix degrades faster than the rest of the matrix at or toward its surface due to an accumulation of trapped acidic o ligomers[13,14,15,16] This accumulation of oligomers results in the development of a highly acidic core at the center of the microparticle matrix. The acidic core microenvironment of PLGA microparticles has been evaluated[17,18,19]; the first study to visualize, measure, and monitor the change in internal pH of individual drug-free microparticles over a period of time was done by the Langer group[14] They used a direct approach to quantitatively evaluate the spatial distribution of the intraparticle acidic environment under physiological conditions (37 °C, phosphate buffered saline (PBS) solution). The particles encapsulated acidic or basic bioactive compounds which alters particle behavior; and, the studies do not include a prolonged evaluation of swelling behavior
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