title: Preparation and characterization of folate conjugated N-trimethyl chitosan nanoparticles as protein carrier targeting folate receptor: in vitro studies.
abstract: Folate conjugated N-trimethyl chitosan (folate-TMC) was synthesized and characterized using Fourier transform infrared (FTIR) and (1)H spectroscopy. The fluorescein isothiocyanate conjugated bovine serum albumin (FITC-BSA) loaded TMC-nanoparticle (FB-TMC-NP) and FITC-BSA loaded folate-TMC-nanoparticle (FB-f-TMC-NP) were prepared by ionic cross-linking of TMC or folate-TMC with sodium alginate. Single factor analysis method was used to optimize the formulation of nanoparticles. The encapsulating efficiencies of FB-TMC-NP and FB-f-TMC-NP produced by optimal formulation were 98.3 +/- 1.9% and 98.7 +/- 2.7% (n=3), respectively. In addition, the mean diameters of FB-TMC-NP and FB-f-TMC-NP were 184.3 +/- 8.3 nm and 176.1 +/- 5.0 nm (n = 3), respectively. Transmission electron microscope (TEM) showed that the nanoparticles were of spherical shapes. The intracellular uptake of FB-f-TMC-NP by SKOV3 cells (folate receptor overexpressing cells) was 3.7-fold more than that of FB-TMC-NP and could be inhibited by the presence of 1 mM folate in the culture medium, although there was no significant difference between the intracellular uptake of FB-f-TMC-NP in A549 cells (folate receptor-deficient cells) and that of FB-TMC-NP in the same cells. In conclusion, the enhancement of cellular uptake of FB-f-TMC-NP by SKOV3 cells in a specific way was attributed to the folate receptor-mediated endocytosis. FB-TMC-NP was a promising carrier for protein.
authors.affiliation: West China Pharmacy School, Sichuan University, Chengdu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cai
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Song
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Chen
authors.forename: Yueqi
authors.initials: Y
authors.lastname: Bi
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Li
authors.forename: Shixiang
authors.initials: S
authors.lastname: Hou
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D010316:Particle Size; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D002352:Carrier Proteins; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; C118071:N-trimethyl chitosan chloride; D011956:Receptors, Cell Surface; D012710:Serum Albumin, Bovine; D048271:Chitosan; D005492:Folic Acid; D016650:Fluorescein-5-isothiocyanate