Application of liposome-encapsulated hydroxycamptothecin in the prevention of epidural scar formation in New Zealand white rabbits

BACKGROUND CONTEXT: Epidural adhesion and fibrosis attribute to the prevalence of pain in normal wound healing after laminectomy surgery. Hydroxycamptothecin (HCPT), an antitumor drug, has proved to be effective in preventing fibroblast proliferation and reducing epidural adhesion after laminectomy in vivo animal study. However, HCPT's disadvantages, such as poor solubility and short half-life, limit its application clinically. Compared with HCPT, the liposome-encapsulated HCPT (L-HCPT) could reduce epidural fibrosis by preventing the proliferation of fibroblast in the scar tissues with longer half-life and increased solubility. PURPOSE: To evaluate the suitability of L-HCPT in the laminectomy models on rabbits and to explore the mechanisms in the prevention of epidural scar formation. STUDY DESIGN: An original investigation that characterizes the novel delivery system in the combinational application of HCPT and liposome (L-HCPT). PATIENT SAMPLE: The sample comprises 24 mature New Zealand white adult rabbits. METHODS: Lumbar laminectomies at L4 and L6 with an L5 disc injury were performed on 24 mature New Zealand white adult rabbits. The rabbits were then randomized into three groups. In Group I, the laminectomy site was treated with a cotton pad soaked with HCPT solution (1 mg/mL) for 5 minutes (HCPT group) and was flushed with saline completely. In Group II, 1 mL of L-HCPT was seeded on the laminectomy area (L-HCPT group). In Group III, the laminectomy area was flushed with saline before wound closure (control group). After 28 days, the animals underwent magnetic resonance imaging. The animals were euthanized; the spinal section was removed for macroscopic evaluation, and hydroxyproline in the scar tissue was quantified. RESULTS: Operation in all the animals yielded a reproducible laminectomy, without complication or mortality. In the laminectomy sites treated with L-HCPT, the dura mater was clean without any evident adhesion. Magnetic resonance imaging analysis implied that L-HCPT treatment could reduce the epidural scar significantly compared with saline control group, which was further proved by the decreased concentration of hydroxyproline in the scar tissues. CONCLUSION: These results demonstrate that the treatment of postlaminectomy wounds in rabbits with L-HCPT reduces the severity of adhesion. (C) 2011 Elsevier Inc. All rights reserved.