Inhibition of cell proliferation by mitomycin C incorporated into P(HEMA) hydrogels.
OBJECTIVE
The technique of mitomycin C (MMC) drug delivery and its application in glaucoma surgery are not standardized with resultant inconsistencies in the results. Also, one time application of MMC does not seem to have the same efficacy after glaucoma drainage device surgeries compared with trabeculectomies. This preliminary study examined the efficacy of a slow release form of MMC for its ability to inhibit cell proliferation in vitro.


METHODS
MMC was incorporated into 1% P(HEMA) hydrogels using a redox polymerization method. For some experiments, unreacted low molecular weight components were removed from the hydrogels before the MMC was incorporated. Sterile disks (8 mm) of each polymer sample were affixed to 60 mm tissue culture dishes, and the dishes were inoculated with COS-1 cells or early passage human conjunctival fibroblasts. After 7 days in culture, the number of cells in each dish was determined. Cell morphology was assessed in replicate cultures after fixation and staining.


RESULTS
Hydrogels with unreacted low molecular weight components slowed cell proliferation and induced morphologic changes. Early passage human conjunctival fibroblasts were more sensitive than COS-1 cells both to intrinsic contaminants in the hydrogels and to incorporated MMC. Once contaminants had been removed, MMC-loaded hydrogels inhibited conjunctival fibroblast proliferation in a dose-dependent fashion, with an IC50 of approximately 0.15 mg/g polymer.


CONCLUSIONS
This study demonstrates that a slow release form of MMC can inhibit cell proliferation in vitro. Future experiments will focus upon the efficacy of this polymer-bound form during in vivo wound healing.
Blake
Diane A
DA
Department of Biochemistry, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Sahiner
Nurettin
N
John
Vijay T
VT
Clinton
Antoine D
AD
Galler
Korianne E
KE
Walsh
Molly
M
Arosemena
Analisa
A
Johnson
Pamela Y
PY
Ayyala
Ramesh S
RS
D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects / Q000648:ultrastructure*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D018463:Filtering Surgery / Q000295:instrumentation; D005901:Glaucoma / Q000601:surgery; D020327:Glaucoma Drainage Implants; D006801:Humans; D020100:Hydrogels; D066298:In Vitro Techniques; D008297:Male; D008689:Methacrylates; D016685:Mitomycin / Q000008:administration & dosage*; D019384:Nucleic Acid Synthesis Inhibitors / Q000008:administration & dosage*; D010784:Photomicrography
D020100:Hydrogels; D008689:Methacrylates; D019384:Nucleic Acid Synthesis Inhibitors; D016685:Mitomycin; C005044:hydroxyethyl methacrylate