[In vitro drug release from a mitomycin C delivery system and its effect against scar tissue adhesion in vivo].

Abstract

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.

CONCLUSION:

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.

• Authors: Yu Zhang, Qing-shui Yin, Chu-song Zhou, Gang-biao Jiang, Yu Zhang
• Journal: Nan fang yi ke da xue xue bao = Journal of Southern Medical University (Nan Fang Yi Ke Da Xue Xue Bao) Vol. 28 Issue 9 Pg. 1568-72 (Aug 2008) ISSN: 1673-4254 [Print] China
• PMID: 18819869 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Polyethylenes
• Succinates
• poly(ethylene succinate)
• Polyethylene Glycols
• Mitomycin
• Chitosan

Topics

• Animals
• Chitosan (chemistry)
• Drug Delivery Systems
• Intervertebral Disc (drug effects, physiopathology, surgery)
• Mitomycin (administration & dosage, chemistry)
• Polyethylene Glycols (chemistry)
• Polyethylenes (chemistry)
• Rats
• Rats, Sprague-Dawley
• Succinates (chemistry)
• Tissue Adhesions (prevention & control)