title: Design and formulation of trimethylated chitosan-graft-poly(ε-caprolactone) nanoparticles used for gene delivery.
abstract: The ideal gene polyplexes should have a subtle balance between polyplex stability to protect DNA against nucleases, and polyplex instability to permit DNA dissociation inside cells. In this research, low molecular weight trimethylated chitosan was chemically modified with poly(ε-caprolactone). Owing to the amphiphilic character, trimethylated chitosan-graft-poly(ε-caprolactone) (TMC-g-PCL) formed nanoparticles in aqueous media. TMC-g-PCL nanoparticles could effectively condense pDNA into polyplexes about 200 nm in size. The TMC-g-PCL/DNA polyplexes were stable in physiological salt condition and showed high uptake efficiency probably due to the increasing cell membrane-carrier interaction as a result of hydrophobic modification. However, the high degree of quaternization influenced the buffer capacity of TMC-g-PCL and led to a reduction in the release from the lysosomes. By adding chloroquine to exclude the limitation of lysosome escape, the transfection efficiency of TMC-g-PCL/DNA polyplexes was similar to that of PEI/DNA polyplexes. This study demonstrated the potential of TMC-g-PCL/DNA nanoparticles as an efficient carrier for gene delivery.
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: San
authors.initials: S
authors.lastname: Tang
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Huang
authors.forename: Haiwen
authors.initials: H
authors.lastname: Zhang
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Hu
authors.forename: Hongliang
authors.initials: H
authors.lastname: Jiang
mesh_terms: D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D015195:Drug Design; D004705:Endocytosis; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000378:metabolism; D008745:Methylation; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D055672:Static Electricity; D014162:Transfection / Q000379:methods*
chemical_list: D004337:Drug Carriers; D011091:Polyesters; C016240:polycaprolactone; D004247:DNA; D048271:Chitosan
keywords: Nanoparticles; Non-viral gene delivery; Poly(ɛ-caprolactone); Trimethylated chitosan