Engineering of recombinant spider silk proteins allows defined uptake and release of substances

J Pharm Sci. 2015 Mar;104(3):988-94. doi: 10.1002/jps.24300. Epub 2014 Dec 27.

Abstract

Drug delivery carriers stabilize drugs and control their release, expanding the therapeutic window, and avoiding side effects of otherwise freely diffusing drugs in the human body. Materials used as carrier vehicles have to be biocompatible, biodegradable, nontoxic, and nonimmunogenic. Previously, particles made of the recombinant spider silk protein eADF4(C16) could be effectively loaded with positively and neutrally charged model substances. Here, a new positively charged variant thereof, named eADF4(κ16), has been engineered. Its particle formation is indistinguishable to that of polyanionic eADF4(C16), but in contrast polycationic eADF4(κ16) allows incorporation of negatively charged substances. Both high-molecular-weight substances, such as nucleic acids, and low-molecular-weight substances could be efficiently loaded onto eADF4(κ16) particles, and release of nucleic acids was shown to be well controlled.

Keywords: DNA/oligonucleotide delivery; biodegradable polymers; biomaterials; biotechnology; drug delivery system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemistry, Pharmaceutical
  • Drug Carriers*
  • Fibroins / chemistry*
  • Fibroins / genetics
  • Fibroins / metabolism
  • Fluoresceins / chemistry*
  • Fluoresceins / metabolism
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / metabolism
  • Gene Transfer Techniques
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Molecular Weight
  • Nucleic Acids / chemistry*
  • Nucleic Acids / metabolism
  • Protein Binding
  • Protein Engineering*
  • Recombinant Proteins / chemistry
  • Solubility
  • Spiders*
  • Surface Properties
  • Technology, Pharmaceutical / methods*

Substances

  • Drug Carriers
  • Fluoresceins
  • Fluorescent Dyes
  • Nucleic Acids
  • Recombinant Proteins
  • 6-carboxyfluorescein
  • Fibroins