a Department of General Surgery , The Affiliated Hospital of Yangzhou University, Yangzhou University , Yangzhou , P. R. China.
b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases , Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , P. R. China.
Drug Deliv. 2018 Nov;25(1):1642-1651. doi: 10.1080/10717544.2018.1497105.
Osteosarcoma is among the most common malignant bone tumors in human skeletal system. The conventional treatment of osteosarcoma mainly consists of combining neoadjuvant chemotherapy with surgical approach. However, it is crucial to design an artificial implant that possesses excellent biomechanical properties and is capable of sustaining local release of chemotherapeutics. In this study, we envision that the highly efficient combination of gemcitabine (GEM) hydrochloride loaded liposomes with gelatin methacryloyl (GelMA) of in situ photocrosslinkable hydrogel will lead to a multifunctional implant with unique antitumor, mechanical, and biodegradable properties. A sustained controlled release was observed; more specifically, the release of GEM in vitro lasted for 4 days long. Furthermore, its capability in killing MG63 cells was further explored by using the lixivium of GEM-Lip@Gel and GEM-GelMA hydrogel in vitro (composite hydrogel by GEM loaded liposomes blending with GelMA, short for GEM-Lip@Gel), which agreed with the drug release outcome. In addition, these hydrogel showed excellent ability in inhibiting osteosarcoma in vivo by Balb/c mice bearing MG63 cells. Therefore, GEM-loaded lipo-hydrogel certainly has presented itself as a promising strategy for the development of implant in the field of osteosarcoma treatment.
骨肉瘤是人类骨骼系统中最常见的恶性骨肿瘤之一。骨肉瘤的传统治疗主要包括新辅助化疗联合手术治疗。然而,设计一种具有优异生物力学性能并能够持续局部释放化疗药物的人工植入物至关重要。在本研究中,我们设想将盐酸吉西他滨(GEM)负载的脂质体与可原位光交联的明胶甲基丙烯酰(GelMA)水凝胶高效结合,将导致具有独特抗肿瘤、机械和可生物降解特性的多功能植入物。观察到持续的控制释放;更具体地说,体外释放 GEM 持续了 4 天。此外,通过使用 GEM 负载脂质体与 GelMA 混合的复合水凝胶(GEM-Lip@Gel,简称 GEM-Lip@Gel)的浸提液在体外进一步探索了其杀死 MG63 细胞的能力,这与药物释放结果一致。此外,这些水凝胶在携带 MG63 细胞的 Balb/c 小鼠体内抑制骨肉瘤方面表现出优异的能力。因此,载药脂质体水凝胶肯定为骨肉瘤治疗领域植入物的发展提供了一种有前途的策略。