Biodegradation, biocompatibility, and drug delivery in poly(ω-pentadecalactone-co-p-dioxanone) copolyesters

Biomaterials. 2011 Sep;32(27):6646-54. doi: 10.1016/j.biomaterials.2011.05.046.

Abstract

Poly(ω-pentadecalactone-co-p-dioxanone) [poly(PDL-co-DO)] copolyesters are copolymers of an isodimorphic system, which remain semicrystalline over the whole range of compositions. Here, we evaluated enzymatically synthesized poly(PDL-co-DO) copolymers as new materials for biomedical applications. In vivo experiments using mice, showed that the copolyesters are well tolerated, with tissue responses that are comparable to poly(p-dioxanone). In addition, the copolymers were found to degrade hydrolytically at controlled rates over a period of several months under physiological conditions. The poly(PDL-co-DO) copolymers with up to 69 mol% DO units were successfully transformed to free-standing nanoparticles that are capable of encapsulating an anticancer drug, doxorubicin, or a polynucleotide, siRNA. Drug- or siRNA-loaded nanoparticles exhibited controlled and continuous release of agent over many weeks. In addition, siLUC-encapsulated poly(PDL-co-DO) nanoparticles were active in inhibiting luciferase gene expression in LUC-RKO cells. Because of substantial differences in structure and hydrophobicity between PDL and DO units, poly(PDL-co-DO) biodegradation rate and physical properties can be tuned over a wide range depending on the copolymer composition. Our results demonstrate that the semicrystalline and biodegradable poly(PDL-co-DO) copolyesters are promising biomaterials to serve as drug carriers, as well as potential raw materials for constructing bioabsorbable sutures and other medical devices.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry*
  • Biodegradation, Environmental / drug effects
  • Dioxanes / chemical synthesis
  • Dioxanes / chemistry*
  • Doxorubicin / pharmacology
  • Drug Delivery Systems / methods*
  • Foreign-Body Reaction / pathology
  • Gene Expression / drug effects
  • Gene Silencing / drug effects
  • Hydrolysis / drug effects
  • Luciferases / genetics
  • Luciferases / metabolism
  • Materials Testing*
  • Mice
  • Molecular Weight
  • Nanoparticles / ultrastructure
  • Particle Size
  • Polyesters / chemical synthesis
  • Polyesters / chemistry*
  • RNA, Small Interfering / metabolism
  • Spermidine / chemistry

Substances

  • Biocompatible Materials
  • Dioxanes
  • Polyesters
  • RNA, Small Interfering
  • poly(omega-pentadecalactone-co-p-dioxanone)
  • Doxorubicin
  • Luciferases
  • Spermidine