[In vitro drug release from a mitomycin C delivery system and its effect against scar tissue adhesion in vivo].
OBJECTIVE
To develop a chitosan (CH)/polyethylene glycols succinate acid (PEG-SA)-mediated mitomycin C (MMC) delivery system and investigate its drug release characteristics in vitro and its effect against scar tissue adhesion in vivo.


METHODS
Mitomycin C loading in the composite CH/PEG-SA/MMC films was determined using ultraviolet. The freeze-dried films were dispersed in 1 ml PBS (pH7.4) and mitomycin C release in vitro was determined according to the mitomycin C concentration-UV value standard curve. The influence of the film structure on the drug release was evaluated. The drug delivery system was then implanted in SD rats, and 4 weeks later, immunohistochemical and histological examinations were carried out to assess the therapeutic effect on epidural scar tissue.


RESULTS
The linear regression equation of the mitomycin C concentration-UV value standard curve was y=0.593x(3)-2.563x(2)+25.944x-0.236 (R(2)=1.000). The film demonstrated good drug delivery capability, and 20 mg of the samples in PBS showed a peak mitomycin C release after 12 days of 14.9616 microg/ml, which was higher than the ID(50) of mitomycin C (10.4713 microg/l) to the fibroblasts. On days 18 and 32, another two drug release peaks occurred (14.4824 microg/ml and 11.4092 microg/ml, respectively), followed by maintenance of slow release. Till day 60, the accumulative mitomycin release reached 0.1793 microg/ml, and the loaded drug was ultimately completely released. Significant differences were noted in the hydroxyproline content in the scar tissues of different groups (F=12.085, P=0.000), and the CH/PEG-SA/MMC DDS reduced the amount of scar tissue and promoted its orderly alignment to control potential scar hyperplasia that may compress the spinal cord and nerve roots.


CONCLUSIONS
The composite film for drug delivery possesses good flexibility and mechanical properties and allows sustained drug release of mitomycin C to prevent epidural scar tissue adhesion following lumbar laminectomy.
Zhang
Yu
Y
Department of Orthopedics, Guangzhou General Hospital of Guangzhou Command, Guangzhou, China. zhangyu1980cmu@yahoo.com.cn
Yin
Qing-shui
QS
Zhou
Chu-song
CS
Jiang
Gang-biao
GB
Zhang
Yu
Y
D000818:Animals; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems; D007403:Intervertebral Disc / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery; D016685:Mitomycin / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011095:Polyethylenes / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013386:Succinates / Q000737:chemistry; D000267:Tissue Adhesions / Q000517:prevention & control*
D011095:Polyethylenes; D013386:Succinates; C443715:poly(ethylene succinate); D011092:Polyethylene Glycols; D016685:Mitomycin; D048271:Chitosan