Li Ruixiu, Song Yunmei, Fouladian Paris, Arafat Mohammad, Chung Rosa, Kohlhagen Jarrod, Garg Sanjay
Pharmaceutical Innovation and Development (PIDG) Group, Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia.
Applied Chemistry and Translational Biomaterials (ACTB) Group, Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia.
Pharmaceutics. 2021 Mar 31;13(4):471. doi: 10.3390/pharmaceutics13040471.
A novel drug delivery system preventing Glioblastoma multiforme (GBM) recurrence after resection surgery is imperatively required to overcome the mechanical limitation of the current local drug delivery system and to offer personalised treatment options for GBM patients. In this study, 3D printed biodegradable flexible porous scaffolds were developed via Fused Deposition Modelling (FDM) three-dimensional (3D) printing technology for the local delivery of curcumin. The flexible porous scaffolds were 3D printed with various geometries containing 1, 3, 5, and 7% (/) of curcumin, respectively, using curcumin-loaded polycaprolactone (PCL) filaments. The scaffolds were characterised by a series of characterisation studies and in vitro studies were also performed including drug release study, scaffold degradation study, and cytotoxicity study. The curcumin-loaded PCL scaffolds displayed versatile spatiotemporal characteristics. The polymeric scaffolds obtained great mechanical flexibility with a low tensile modulus of less than 2 MPa, and 4 to 7-fold ultimate tensile strain, which can avoid the mechanical mismatch problem of commercially available GLIADEL wafer with a further improvement in surgical margin coverage. In vitro release profiles have demonstrated the sustained release patterns of curcumin with adjustable release amounts and durations up to 77 h. MTT study has demonstrated the great cytotoxic effect of curcumin-loaded scaffolds against the U87 human GBM cell line. Therefore, 3D printed curcumin-loaded scaffold has great promise to provide better GBM treatment options with its mechanical flexibility and customisability to match individual needs, preventing post-surgery GBM recurrence and eventually prolonging the life expectancy of GBM patients.
迫切需要一种新型药物递送系统来预防多形性胶质母细胞瘤（GBM）切除术后的复发，以克服当前局部药物递送系统的机械限制，并为GBM患者提供个性化治疗方案。在本研究中，通过熔融沉积建模（FDM）三维（3D）打印技术开发了用于局部递送姜黄素的3D打印可生物降解柔性多孔支架。使用负载姜黄素的聚己内酯（PCL）细丝，3D打印出具有不同几何形状的柔性多孔支架，分别含有1%、3%、5%和7%（/）的姜黄素。通过一系列表征研究对支架进行了表征，并进行了体外研究，包括药物释放研究、支架降解研究和细胞毒性研究。负载姜黄素的PCL支架表现出多样的时空特性。聚合物支架具有很大的机械柔韧性，拉伸模量低至小于2MPa，极限拉伸应变提高了4至7倍，这可以避免市售GLIADEL薄片的机械不匹配问题，并进一步改善手术切缘覆盖。体外释放曲线表明姜黄素具有持续释放模式，释放量和持续时间可调节，长达77小时。MTT研究表明负载姜黄素的支架对U87人GBM细胞系具有很大的细胞毒性作用。因此，3D打印负载姜黄素的支架因其机械柔韧性和可定制性以满足个体需求，有望为GBM提供更好的治疗方案，预防术后GBM复发并最终延长GBM患者的预期寿命。
