Effects of chemical composition on the in vitro degradation of micelles prepared from poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) block copolymers - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Polymer Degradation and Stability Année : 2018

Effects of chemical composition on the in vitro degradation of micelles prepared from poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) block copolymers

Chenglong Li
  • Fonction : Auteur
Rongye Li
  • Fonction : Auteur
Yuandou Wang
  • Fonction : Auteur
Laishun Xi
  • Fonction : Auteur
S.M. Li

Résumé

In this work, a series of poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) diblock copolymers with relatively short PLGA blocks were synthesized by ring-opening polymerization of D,L-lactide and glycolide in the presence of monomethoxy PEG with Mn of 2000. Spherical micelles were obtained by self-assembly of copolymers using direct dissolution method. The degradation of the micelles was investigated under in vitro conditions at 37 degrees C. The effects of chemical composition on micelle degradation were evaluated from NMR, GPC, DLS and TEM measurements. The molar mass of copolymers constantly decreases during degradation in all cases. The copolymers with longer hydrophobic PLGA blocks exhibit larger molar mass decrease rate since only the PLGA block is degradable. Meanwhile, the molar mass distribution remains almost unchanged, in agreement with random chain cleavage. NMR spectra show that the final degradation products are lactic acid and glycolic acid. A pH decrease is also detected during degradation. The size of the micelle depends on the chemical composition of copolymers. Micelle size is smaller for copolymers with longer hydrophobic PLGA blocks because of more compact core structure. With the hydrolysis of the PLGA blocks, the structure of micelles becomes looser, and the micelle size exhibits a sharp increase after a lag time. At the later stage of degradation, the size of micelles decreases as they become unstable and could collapse. The micelle structure could be clearly distinguished after 45 days degradation for copolymers with longer PLGA blocks, whereas those with shorter PLGA blocks lost the structural integrity. It is also noteworthy that the LA/GA ratio has little effect on the degradation of PLGA-PEG copolymer micelles, which may be related to the amorphous structure of PLGA block and the relatively short block length. These findings should be helpful for the conception of drug delivery systems based on PLGA-PEG micelles.

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Chimie
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Dates et versions

hal-01968123 , version 1 (02-01-2019)

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Citer

Feng Su, Chenglong Li, Rongye Li, Peng Yun, Yuandou Wang, et al.. Effects of chemical composition on the in vitro degradation of micelles prepared from poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) block copolymers. Polymer Degradation and Stability, 2018, 158, pp.202-211. ⟨10.1016/j.polymdegradstab.2018.11.007⟩. ⟨hal-01968123⟩
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