Thiol-modified chitosan sulfate nanoparticles for protection and release of basic fibroblast growth factor.
A series of chitosan (CS) derivatives, the 6-O-carboxymethylchitosan (6-O-CC), 2-N sulfated 6-O-carboxymethylchitosan (N-SOCC) and the 2-N and 3,6-O sulfated 6-O-carboxymethyl chitosan (N,O-SOCC) were synthesized in this study. The chemical structures and the degrees of substituted carboxymethyl and sulfate groups of the synthesized compounds were respectively determined by FT-IR spectra and elemental analysis. N,O-SOCC displayed the highest protective efficiency for basic fibroblast growth factor (bFGF) as examined by the L929 fibroblast culture test and docking simulation. N,O-SOCC-4-thio-butylamidine (TBA) conjugates prepared by modification of N,O-SOCC with 2-iminothiolane were in situ cross-linkable. The degrees of thiol substitution of the 2-iminothiolane modified N,O-SOCC polymers were determined to be in the ranges of 45.9 +/- 3.7 and 415.6 +/- 12.5 micromol SH/g SOCC by quantifying the amount of thiol groups on the thiolated polymers with Ellman's reagent. The 2-iminothiolane modified N,O-SOCC and CS complex could be used for preparing nanoparticles by a polyelectrolyte self-assembly method, and the release of bFGF from the nanoparticles was successfully controlled. L929 fibroblast culture tests showed that the thiol modified N,O-SOCC/CS nanoparticles could effectively protect bFGF from inactivation over a 120 h period. The results of this study suggest that the thiol modified N,O-SOCC/CS nanoparticles may be useful as novel materials for specific delivery of bFGF with mitogenic activity.
Ho
Yi-Cheng
YC
Department of Biotechnology, Vanung University, Chung-Li, Taiwan, Republic of China.
Wu
Shao-Jung
SJ
Mi
Fwu-Long
FL
Chiu
Ya-Lin
YL
Yu
Shu-Huei
SH
Panda
Nilendu
N
Sung
Hsing-Wen
HW
D000818:Animals; D002478:Cells, Cultured; D048271:Chitosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000494:pharmacology; D013997:Time Factors
C504164:O-carboxymethylchitosan; D013438:Sulfhydryl Compounds; C480355:chitosan sulfate; D016222:Fibroblast Growth Factor 2; D048271:Chitosan