Chai Feng, Abdelkarim Mohamed, Laurent Thomas, Tabary Nicolas, Degoutin Stephanie, Simon Nicolas, Peters Fabian, Blanchemain Nicolas, Martel Bernard, Hildebrand Hartmut F
Université Lille Nord de France, Lille, France; Groupe de Recherche sur les Biomatériaux (U 1008 INSERM) Université Lille 2-Faculté de Médecine, Lille, France.
J Biomed Mater Res B Appl Biomater. 2014 Aug;102(6):1130-9. doi: 10.1002/jbm.b.33094. Epub 2013 Dec 18.
The progress in bone cancer surgery and multimodal treatment concept achieve only modest improvement in the overall survival, due to failure in clearing out residual cancer cells at the surgical margin and extreme side-effects of adjuvant postoperative treatments. Our study aims to propose a new method based on cyclodextrin polymer (polyCD) functionalized hydroxyapatite (HA) for achieving a high local drug concentration with a sustained release profile and a better control of residual malignant cells via local drug delivery and promotion of the reconstruction of bone defects. PolyCD, a versatile carrier for therapeutic molecules, can be incorporated into HA (bone regeneration scaffold) through thermal treatment. The parameters of polyCD treatment on the macroporous HA (porosity 65%) were characterized via thermogravimetric analysis. Good cytocompatibility of polyCD functionalized bioceramics was demonstrated on osteoblast cells by cell vitality assay. An antibiotic (gentamicin) and an anticancer agent (cisplatin) were respectively loaded on polyCD functionalized bioceramics for drug release test. The results show that polyCD functionalization leads to significantly improved drug loading quantity (30% more concerning gentamicin and twice more for cisplatin) and drug release duration (7 days longer concerning gentamicin and 3 days longer for cisplatin). Conclusively, this study offers a safe and reliable drug delivery system for bioceramic matrices, which can load anticancer agents (or/and antibiotics) to reduce local recurrence (or/and infection).
由于在手术切缘清除残留癌细胞失败以及辅助术后治疗的极端副作用，骨癌手术和多模式治疗理念的进展仅使总体生存率有适度提高。我们的研究旨在提出一种基于环糊精聚合物（聚环糊精）功能化羟基磷灰石（HA）的新方法，通过局部药物递送和促进骨缺损修复，实现高局部药物浓度、持续释放以及更好地控制残留恶性细胞。聚环糊精是一种多功能治疗分子载体，可通过热处理掺入HA（骨再生支架）中。通过热重分析对聚环糊精处理大孔HA（孔隙率65%）的参数进行了表征。通过细胞活力测定法在成骨细胞上证明了聚环糊精功能化生物陶瓷具有良好的细胞相容性。将一种抗生素（庆大霉素）和一种抗癌剂（顺铂）分别负载在聚环糊精功能化生物陶瓷上进行药物释放测试。结果表明，聚环糊精功能化导致药物负载量显著提高（庆大霉素提高30%，顺铂提高两倍）以及药物释放持续时间延长（庆大霉素延长7天，顺铂延长3天）。总之，本研究为生物陶瓷基质提供了一种安全可靠的药物递送系统，该系统可负载抗癌剂（或/和抗生素）以减少局部复发（或/和感染）。
