title: Synthesis of a novel CS-g-MMCs conjugate and the inhabitation on the proliferation of Tenon's capsule fibroblasts in vitro.
abstract: A novel anti-proliferative macromolecular conjugate, CS-g-MMCs, was synthesized in order to decrease the cytotoxicity of Mitomycin C (MMC) which was a traditional anti-proliferative agent of fibroblast in trabeculectomy. The structure of CS-g-MMCs was characterized by (1)H NMR, FT-IR spectroscopy and GPC analysis. The grafting degree (dg) of MMC onto chitosan (CS) was determined to be in the range of 2.8-11.3%, which could be controlled by variation of the molar ratios of MMC to oxidized chitosan (CS-CHO). In the drug release profiles of CS-g-MMCs in vitro, an initial burst followed by slow leakage was observed, and addition of acid or lysozyme obviously accelerated the MMC release. The MTS assay indicated that CS-CHO of 8 mg/ml has no cytotoxicity against human Tenon's capsule fibroblasts (HTCFs). The inhibition of HTCFs proliferation by CS-g-MMCs increased along with increasing the dg of conjugate. The CS-g-MMCs also caused the apoptosis of HTCFs and interfered in the active DNA synthesis in HTCFs. Furthermore, the expression of a-SMA at gene and protein levels were obviously lower when HTCFs were treated with CS-g-MMCs, as compared to MMC or blend of MMC/CS-CHO (p<0.05). Our results primarily demonstrated that the CS-g-MMCs conjugates have low cytotoxicity and have the effect to inhibit fibroblast proliferation.
authors.affiliation: DSAPM Lab, PCFM Lab, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Duan
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Li
authors.forename: Liangqi
authors.initials: L
authors.lastname: Ouyang
authors.forename: Daping
authors.initials: D
authors.lastname: Quan
authors.forename: Qiongjuan
authors.initials: Q
authors.lastname: Zheng
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.forename: Qianying
authors.initials: Q
authors.lastname: Gao
authors.forename: Jian
authors.initials: J
authors.lastname: Ge
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000963:Antimetabolites / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D002850:Chromatography, Gel; D004261:DNA Replication / Q000187:drug effects; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D009113:Muramidase / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D058475:Tenon Capsule / Q000187:drug effects* / Q000473:pathology; D055815:Young Adult
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000963:Antimetabolites; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D016685:Mitomycin; D048271:Chitosan; D009113:Muramidase