Biodegradable Polyester of Poly (Ethylene glycol)-sebacic Acid as a Backbone for β -Cyclodextrin-polyrotaxane: A Promising Gene Silencing Vector

Curr Gene Ther. 2019;19(4):274-287. doi: 10.2174/1566523219666190808094225.


Background: Polyrotaxane, a macromolecular interlocked assembly, consisting of cyclodextrin has excellent inclusion capabilities and functionalization capacity, which makes it a versatile material as a vector for gene delivery applications.

Objective: A biodegradable linear aliphatic polyester axle composed of Polyethylene Glycol (PEG) and Sebacic Acid (SA) was used to fabricate the β-Cyclodextrin (β-CD) based polyrotaxane as a cationic polymeric vector and evaluated for its potential gene silencing efficiency.

Methods: The water-soluble aliphatic polyester was synthesized by the solvent esterification process and characterized using viscometry, GPC, FT-IR and 1H NMR spectroscopy. The synthesized polyester was further evaluated for its biodegradability and cellular cytotoxicity. Hence, this water-soluble polyester was used for the step-wise synthesis of polyrotaxane, via threading and blocking reactions. Threading of β-CD over PEG-SA polyester axle was conducted in water, followed by end-capping of polypseudorotaxane using 2,4,6-trinitrobenzenesulfonic acid to yield polyester-based polyrotaxane. For gene delivery application, cationic polyrotaxane (PRTx+) was synthesized and evaluated for its gene loading and gene silencing efficiency.

Results and discussion: The resulting novel macromolecular assembly was found to be safe for use in biomedical applications. Further, characterization by GPC and 1H NMR techniques revealed successful formation of PE-β-CD-PRTx with a threading efficiency of 16%. Additionally, the cellular cytotoxicity assay indicated biosafety of the synthesized polyrotaxane, exploring its potential for gene delivery and other biomedical applications. Further, the biological profile of PRTx+: siRNA complexes was evaluated by measuring their zeta potential and gene silencing efficiency, which were found to be comparable to Lipofectamine 3000, the commercial transfecting agent.

Conclusion: The combinatory effect of various factors such as biodegradability, favourable complexation ability, near zero zeta potentials, good cytotoxicity properties of poly (ethylene glycol)-sebacic acid based β-Cyclodextrin-polyrotaxane makes it a promising gene delivery vector for therapeutic applications.

Keywords: GFP; Polyester; biodegradation; cyclodextrin; gene silencing; polyrotaxane; siRNA..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclodextrins / chemistry*
  • Decanoic Acids / chemistry*
  • Dicarboxylic Acids / chemistry*
  • Gene Silencing*
  • Gene Transfer Techniques
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • Green Fluorescent Proteins / antagonists & inhibitors*
  • Green Fluorescent Proteins / genetics
  • HeLa Cells
  • Humans
  • Poloxamer / chemistry*
  • Polyesters / chemistry
  • Polyethylene Glycols / chemistry*
  • Polymers
  • RNA, Small Interfering / genetics*
  • Rotaxanes / chemistry*
  • beta-Cyclodextrins / chemistry*


  • Cyclodextrins
  • Decanoic Acids
  • Dicarboxylic Acids
  • Polyesters
  • Polymers
  • RNA, Small Interfering
  • Rotaxanes
  • beta-Cyclodextrins
  • polyrotaxane
  • Poloxamer
  • Green Fluorescent Proteins
  • Polyethylene Glycols
  • sebacic acid