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

Jennifer Walker, Jason Albert, Desheng Liang, Jing Sun, Richard Schutzman, Raj Kumar, Cameron White, Moritz Beck-Broichsitter, Steven P. Schwendeman

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)237-251
Number of pages15
JournalDrug Delivery and Translational Research
Volume13
Issue number1
DOIs
StatePublished - Jan 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022, Controlled Release Society.

Funding

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

FundersFunder number
MilliporeSigma a Business of Merck KGaA
Merck KGaA

    Keywords

    • Controlled drug release
    • Long-term drug release
    • PLGA
    • Polymer in vitro behavior

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