Journal
ACTA BIOMATERIALIA
Volume 65, Issue -, Pages 259-271Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2017.10.043
Keywords
Poly(lactic-co-glycolic acid); Two-photon microscopy; Acidic microclimate; Foreign body response; Sequenced copolymers
Funding
- National Science Foundation [CHE-1410119]
- Division Of Chemistry [1410119] Funding Source: National Science Foundation
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Controlling the backbone architecture of poly(lactic-co-glycolic acid)s (PLGAs) is demonstrated to have a strong influence on the production and release of acidic degradation by-products in microparticle matrices. Previous efforts for controlling the internal and external accumulation of acidity for PLGA microparticles have focused on the addition of excipients including neutralization and anti-inflammatory agents. In this report, we utilize a sequence-control strategy to tailor the microstructure of PLGA. The internal acidic microclimate distributions within sequence-defined and random PLGA microparticles were monitored in vitro using a non-invasive ratiometric two-photon microscopy (TPM) methodology. Sequence defined PLGAs were found to have minimal changes in pH distribution and lower amounts of percolating acidic by-products. A parallel scanning electron microscopy study further linked external morphological events to internal degradation-induced structural changes. The properties of the sequenced and random copolymers characterized in vitro translated to differences in in vivo behavior. The sequence alternating copolymer, poly LG, had lower granulomatous foreign-body reactions compared to random racemic PLGA with a 50:50 ratio of lactic to glycolic acid. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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