Synthesis of polysaccharide-block-polypeptide copolymer for potential co-delivery of drug and plasmid DNA

Macromol Biosci. 2015 Jun;15(6):756-64. doi: 10.1002/mabi.201400454. Epub 2015 Mar 11.

Abstract

A pH-sensitive, biodegradable, and biocompatible polysaccharide-block-polypeptide Copolymer derivative {Ac-Dex-b-PAsp(DET)} is synthetized from acetal-modified dextran (Ac-Dex) and diethylenetriamine (DET) grafted poly(L-aspartic acid) {PAsp(DET)} by using click and aminolysis reaction. The copolymer can self-assemble into cationic nanopaticles for potential co-delivery of plasmid DNA (pEGFP-N3) and anticancer drug (doxorubicin, DOX), by using water/oil/water (w/o/w) emulsion method. Gel retardation assay reveals that pDNA can be effectively complexed into cationic nanoparticles at N/P ratio = 12. In vitro drug release behavior of DOX-NPs and DOX/pDNA-NPs is achieved by using fluorescence spectra and UV-Vis spectra and confocal laser scanning microscopy (CLSM). And, pEGFP-N3-NPs at N/P ratio = 42 presents the considerable potential in cell transfection. Cell viability assay shows that nanoparticles exhibit low cell cytotoxicity. These results suggest that the copolymer has excellent performance and potential for the co-delivery of gene and drugs.

Keywords: co-delivery; drugs; plasmid DNA; polypeptide; polysaccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Dextrans* / chemistry
  • Dextrans* / pharmacology
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacology
  • Drug Delivery Systems*
  • Humans
  • Peptides* / chemistry
  • Peptides* / pharmacology
  • Plasmids* / chemistry
  • Plasmids* / pharmacology
  • Transfection*

Substances

  • Dextrans
  • Peptides
  • polyaspartate
  • Doxorubicin