title: Amino acid grafted chitosan for high performance gene delivery: comparison of amino acid hydrophobicity on vector and polyplex characteristics.
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nursing, and Allied Sciences, North Dakota State University, Fargo, ND 58105, United States.
authors.forename: Buddhadev
authors.initials: B
authors.lastname: Layek
authors.forename: Jagdish
authors.initials: J
authors.lastname: Singh
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D001672:Biocompatible Materials / Q000138:chemical synthesis*; D001692:Biological Transport; D002234:Carbodiimides / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000596:Amino Acids; D001672:Biocompatible Materials; D002234:Carbodiimides; D011108:Polymers; D004247:DNA; D048271:Chitosan