The impact of monomer sequence and stereochemistry on the swelling and erosion of biodegradable poly(lactic-co-glycolic acid) matrices

Biomaterials. 2017 Feb;117:66-76. doi: 10.1016/j.biomaterials.2016.11.037. Epub 2016 Nov 24.


Monomer sequence is demonstrated to be a primary factor in determining the hydrolytic degradation profile of poly(lactic-co-glycolic acid)s (PLGAs). Although many approaches have been used to tune the degradation of PLGAs, little effort has been expended in exploring the sequence-control strategy exploited by nature in biopolymers. Cylindrical matrices and films prepared from a series of sequenced and random PLGAs were subjected to hydrolysis in a pH 7.4 buffer at 37 °C. Swelling ranged from 107% for the random racemic PLGA with a 50:50 ratio of lactic (L) to glycolic (G) units to 6% for the sequenced alternating copolymer poly LG. Erosion followed an inverse trend with the random 50:50 PLGA showing an erosion half-life of 3-4 weeks while poly LG required ca. >10 weeks. Stereosequence was found to play a large role in determining swelling and erosion; stereopure analogs swelled less and were slower to lose mass. Molecular weight loss followed similar trends and increases in dispersity correlated with the onset of significant swelling. The relative proportion of rapidly cleavable G-G linkages relative to G-L/L-G (moderate) and L-L (slow) correlates strongly with the degree of swelling observed and the rate of erosion. The dramatic sequence-dependent variation in swelling, in the absence of a parallel hydrophilicity trend, suggest that osmotic pressure, driven by the differential accumulation of degradation products, plays an important role.

Keywords: Biodegradable polymers; PLGA; Polymer degradation; Polymer erosion; Polymer swelling; Sequenced copolymers.

MeSH terms

  • Absorbable Implants*
  • Biocompatible Materials / analysis*
  • Biocompatible Materials / chemistry*
  • Lactic Acid / analysis*
  • Lactic Acid / chemistry*
  • Materials Testing
  • Molecular Weight
  • Polyglycolic Acid / analysis*
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Structure-Activity Relationship


  • Biocompatible Materials
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid