Hydroxycamptothecin liposomes inhibit collagen secretion and induce fibroblast apoptosis in a postlaminectomy rabbit model

Abstract

To design and attest the role of hydroxycamptothecin liposomes (L-HCPT) as a new delivery system to prevent epidural scar adhesions after laminectomy in a rabbit model. Lumbar laminectomies at L6 were performed on 18 mature male New Zealand rabbits. The rabbits were randomly divided into three groups: (I) a cotton pad soaked with 0.05 % hydroxycamptothecin (HCPT) solution was kept on the laminectomy area for 5 min before the layers were sutured (HCPT group); (II) 25 mg of liposomes containing 0.01 % HCPT was implanted on the laminectomy area (L-HCPT group); and (III) the laminectomy area was flushed with saline (control group). The rabbits were killed 4 weeks after the operation. Macroscopic evaluation and histological analysis of epidural scar adhesion were employed with hematoxylin-eosin and Masson staining, followed by hydroxyproline (Hyp) quantification and magnetic resonance imaging (MRI) of postoperative rabbit scar tissues. The epidural scar area and number of fibroblasts in the scar tissue were also evaluated. In the laminectomy sites of rabbits treated with HCPT or L-HCPT, the dura mater and nerve root were clean without evident scar adhesion. Hyp concentration was significantly lower in these two groups compared with the saline-control group. On the other hand, the MRI of postoperative rabbits showed apparent decreased fibrosis around the dura mater in these two groups compared with the control group. In addition, the epidural scar area and the number of fibroblasts were significantly lower in the two groups compared with the control group. These results demonstrate that the treatment of postlaminectomy wounds with L-HCPT may reduce and prevent the severity of adhesion.