Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Ann Surg Oncol. 2010 Apr;17(4):1203-13. doi: 10.1245/s10434-009-0856-z. Epub 2009 Dec 3.
To evaluate the efficacy of a polymer film designed for prolonged paclitaxel release at surgical margins to prevent local recurrence in non-small-cell lung cancer (NSCLC) following complete surgical resection in a murine model.
Poly(glycerol monostearate co-epsilon-caprolactone) polymer films were prepared with or without 10% (w/w) paclitaxel and characterized for prolonged tumor cytotoxicity in vitro against several NSCLC cell lines including LLC, NCI-H460, and NCI-H292. Films were implanted following complete LLC tumor resection and assessed in vivo for prevention of local tumor recurrence, impact on wound healing, and extent of local drug delivery. Plasma and local tissue concentrations of paclitaxel were compared following systemic administration and film implantation.
The flexible polymeric films eluted paclitaxel over several weeks and remained cytotoxic to LLC, NCI-H460, and NCI-H292 cells in vitro for 50 days, while unloaded films did not impair tumor cell growth. Implanted paclitaxel films prevented local tumor recurrence in vivo in 83.3% of animals, compared with unloaded films (12.5%), systemic (22.2%) or locally administered paclitaxel (0%) (P < 0.005). Although minimal paclitaxel remained in either plasma or tissue 10 days after systemic injection, local paclitaxel concentration at the site of surgical resection was significantly greater (3,000-fold) at 10 days when paclitaxel was locally delivered via films (P = 0.024).
Local application of paclitaxel-loaded polymer films following surgical resection can prevent local tumor recurrence without impairing wound healing.
评估一种用于延长紫杉醇释放的聚合物薄膜在完全手术切除后预防非小细胞肺癌（NSCLC）手术切缘局部复发的疗效，在小鼠模型中。
制备了含有或不含有 10%（w/w）紫杉醇的聚（甘油单硬脂酸酯-co-ε-己内酯）聚合物薄膜，并对其进行了体外延长对包括 LLC、NCI-H460 和 NCI-H292 在内的几种 NSCLC 细胞系的肿瘤细胞毒性进行了特征分析。在完全切除 LLC 肿瘤后植入薄膜，并在体内评估其预防局部肿瘤复发、对伤口愈合的影响以及局部药物输送的程度。比较了全身给药和薄膜植入后紫杉醇在血浆和局部组织中的浓度。
柔性聚合物薄膜在数周内洗脱紫杉醇，并在体外对 LLC、NCI-H460 和 NCI-H292 细胞保持长达 50 天的细胞毒性，而未载药的薄膜不会影响肿瘤细胞的生长。植入的紫杉醇薄膜可预防 83.3%的动物体内局部肿瘤复发，而未载药的薄膜（12.5%）、全身（22.2%）或局部给予紫杉醇（0%）的动物则无局部肿瘤复发（P<0.005）。尽管全身注射后 10 天在血浆或组织中仍残留少量紫杉醇，但在通过薄膜局部给药时，手术切除部位的局部紫杉醇浓度在 10 天时明显更高（3000 倍）（P=0.024）。
在手术切除后局部应用载紫杉醇的聚合物薄膜可以预防局部肿瘤复发，而不会影响伤口愈合。
