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In vitro degradation and erosion behavior of commercial PLGAs used for controlled drug delivery

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Abstract

Copolymers of lactic (or lactide) and glycolic (or glycolide) acids (PLGAs) are among the most commonly used materials in biomedical applications, such as parenteral controlled drug delivery, due to their biocompatibility, predictable degradation rate, and ease of processing. Besides manufacturing variables of drug delivery vehicles, changes in PLGA raw material properties can affect product behavior. Accordingly, an in-depth understanding of polymer-related “critical quality attributes” can improve selection and predictability of PLGA performance. Here, we selected 19 different PLGAs from five manufacturers to form drug-free films, submillimeter implants, and microspheres and evaluated differences in their water uptake, degradation, and erosion during in vitro incubation as a function of L/G ratio, polymerization method, molecular weight, end-capping, and geometry. Uncapped PLGA 50/50 films from different manufacturers with similar molecular weights and higher glycolic unit blockiness and/or block length values showed faster initial degradation rates. Geometrically, larger implants of 75/25, uncapped PLGA showed higher water uptake and faster degradation rates in the first week compared to microspheres of the same polymers, likely due to enhanced effects of acid-catalyzed degradation from PLGA acidic byproducts unable to escape as efficiently from larger geometries. Manufacturer differences such as increased residual monomer appeared to increase water uptake and degradation in uncapped 50/50 PLGA films and poly(lactide) implants. This dataset of different polymer manufacturers could be useful in selecting desired PLGAs for controlled release applications or comparing differences in behavior during product development, and these techniques to further compare differences in less reported properties such as sequence distribution may be useful for future analyses of PLGA performance in drug delivery.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Funding

This study was supported by a fund from MilliporeSigma a Business of Merck KGaA (Darmstadt, Germany).

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Contributions

Material preparation, data collection, and analysis were performed by Jennifer Walker. Data collection and analysis were also performed by Jason Albert, Desheng Liang, Jing Sun, Richard Schutzman, Cameron White, and Raj Kumar. Steven P Schwendeman, Moritz Beck-Broichsitter, Jennifer Walker, and Jason Albert contributed to study conception and design. All authors whose names appear on the submission approved the version to be published.

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Correspondence to Steven P. Schwendeman.

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Supplementary information

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13346_2022_1177_MOESM1_ESM.docx

Supplementary file1 Fig. 1 Lactic content remaining in 50/50 uncapped and end-capped PLGA films as a function of incubation time. (DOCX 93 KB)

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Walker, J., Albert, J., Liang, D. et al. In vitro degradation and erosion behavior of commercial PLGAs used for controlled drug delivery. Drug Deliv. and Transl. Res. 13, 237–251 (2023). https://doi.org/10.1007/s13346-022-01177-8

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  • DOI: https://doi.org/10.1007/s13346-022-01177-8

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