Protein release from water-swellable poly(D,L-lactide-PEG)-b-poly(ϵ-caprolactone) implants

Int J Pharm. 2015 Mar 1;480(1-2):73-83. doi: 10.1016/j.ijpharm.2015.01.007. Epub 2015 Jan 6.

Abstract

In this study, water-swellable multiblock copolymers composed of semi-crystalline poly(ϵ-caprolactone) [PCL] blocks and amorphous blocks consisting of poly(D,L-lactide) (PDLLA) and poly(ethylene glycol) (PEG) [PDLLA-PEG] were synthesized. The block ratio of these [PDLLA-PEG]-b-[PCL] multiblock copolymers was varied and the degradation of implants prepared of these polymers by hot melt extrusion (HME) was compared with implants prepared of [PCL-PEG]-b-[PCL], a copolymer which has been described previously (Stanković et al., 2014). It was shown that the initial degradation rate of the [PDLLA-PEG]-b-[PCL] multiblock copolymers increased with increasing the content of amorphous [PDLLA-PEG] block and that the degradation rate of these multiblock copolymers was faster than that of the [PCL-PEG]-b-[PCL] multiblock copolymers due to rapid degradation of the [PDLLA-PEG] block. Furthermore, the release of the model proteins lysozyme and bovine serum albumin from polymer implants prepared by HME was studied. It was found that the protein release from [PDLLA-PEG]-b-[PCL] copolymers was incomplete, which is not acceptable for any application of these polymers. Besides, [PCL-PEG]-b-[PCL] copolymers showed slow and continuous release. We hypothesize that the incomplete release is explained by an irreversible interaction between the proteins and polymer degradation products or by entrapment of the protein in the hydrophobic and non-swellable polymer matrix that was left after degradation and loss of the hydrophilic [PDLLA-PEG] blocks from the degrading polymer.

Keywords: Bovine serum albumin; Hot melt extrusion; Lysozyme; Polymer degradation; Polymer implants; Protein–polymer interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry, Pharmaceutical / methods
  • Crystallization
  • Delayed-Action Preparations
  • Drug Implants
  • Drug Liberation
  • Hydrophobic and Hydrophilic Interactions
  • Muramidase / administration & dosage
  • Muramidase / chemistry
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*
  • Proteins / administration & dosage*
  • Proteins / chemistry
  • Serum Albumin, Bovine / administration & dosage
  • Serum Albumin, Bovine / chemistry
  • Water / chemistry

Substances

  • Delayed-Action Preparations
  • Drug Implants
  • Polyesters
  • Proteins
  • Water
  • polycaprolactone
  • Serum Albumin, Bovine
  • Polyethylene Glycols
  • poly(lactide)
  • Muramidase