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Curr Gene Ther. 2019 Aug 7. doi: 10.2174/1566523219666190808094225. [Epub ahead of print]

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

Author information

1
Department of Chemical Engineering, Institute of Chemical Technology, Matunga, Mumbai-400 019. India.
2
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai-400 019. India.
3
Polymer Science and Engineering Division, CSIR-National Chemical Laboratory, Pune 411008. India.

Abstract

BACKGROUND:

Polyrotaxane, a macromolecular interlocked assembly, consisting of cyclodextrin has excellent inclusion capabilities and functionalization capacity that makes it 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.

METHOD:

The water soluble aliphatic polyester was synthesized by solvent esterification process and characterized by viscometer, 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 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:

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, suggesting 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 potential gene delivery vector for therapeutic applications.

KEYWORDS:

Biodegradation; Cyclodextrin; GFP; Gene Silencing; Polyester; Polyrotaxane; siRNA

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