Amino acid grafted chitosan for high performance gene delivery: Comparison of amino acid hydrophobicity on vector and polyplex characteristics

Buddhadev Layek, Jagdish Singh

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

To develop a safe, effective, and biocompatible gene delivery vector, a series of hydrophobic amino acid grafted chitosan (AGC) derivatives were synthesized by carbodiimide mediated coupling reaction. Chemical characterization of AGC polymers was performed by NMR and elemental analysis. AGC polymers demonstrated excellent blood compatibility and cell viability, as evaluated by hemolysis and MTT assay, respectively. AGC polymers could effectively bind and condense plasmid DNA (pDNA) to form polyplexes in the size range of 161-263 nm and possessed net cationic charge. The resultant polyplex showed 3.4-5.4-fold greater cellular uptake and 13-30-fold higher transfection efficiency in HEK 293 cells as compared to unmodified chitosan. Moreover, both cellular uptake and transfection efficiency improved with the increasing amino acid hydrophobicity. Hydrophobic amino acid substitution contributed to the enhance pDNA release at cytosolic pH. These data demonstrate AGC polymers as a promising novel nonviral gene delivery vector.

Original languageEnglish (US)
Pages (from-to)485-494
Number of pages10
JournalBiomacromolecules
Volume14
Issue number2
DOIs
StatePublished - Feb 11 2013

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