Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 708 Renmin Road, Suzhou, Jiangsu 215006, PR China; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 708 Renmin Road, Suzhou, Jiangsu 215006, PR China.
Colloids Surf B Biointerfaces. 2015 Jun 1;130:1-9. doi: 10.1016/j.colsurfb.2015.03.058. Epub 2015 Apr 3.
Implantable tissue engineering scaffolds with temporally programmable multi-drug release are recognized as promising tools to improve therapeutic effects. A good example would be one that exhibits initial anti-inflammatory and long-term anti-tumor activities after tumor resection. In this study, a new strategy for self-coated interfacial layer on drug-loaded mesoporous silica nanoparticles (MSNs) based on mussel-mimetic catecholamine polymer (polydopamine, PDA) layer was developed between inorganic and organic matrix for controlling drug release. When the interface PDA coated MSNs were encapsulated in electrospun poly(L-lactide) (PLLA) fibers, the release rates of drugs located inside/outside the interfacial layer could be finely controlled, with short-term release of anti-inflammation ibuprofen (IBU) for 30 days in absence of interfacial interactions and sustained long-term release of doxorubicin (DOX) for 90 days in presence of interfacial interactions to inhibit potential tumor recurrence. The DOX@MSN-PDA/IBU/PLLA hybrid fibrous scaffolds were further found to inhibit proliferation of inflammatory macrophages and cancerous HeLa cells, while supporting the normal stromal fibroblast adhesion and proliferation at different release stages. These results have suggested that the interfacial obstruction layer at the organic/inorganic phase was able to control the release of drugs inside (slow)/outside (rapid) the interfacial layer in a programmable manner. We believe such interface polymer strategy will find applications in where temporally controlled multi-drug delivery is needed.
具有时间可编程多药物释放的可植入组织工程支架被认为是提高治疗效果的有前途的工具。一个很好的例子是，在肿瘤切除后，它表现出初始的抗炎和长期的抗肿瘤活性。在这项研究中，开发了一种新的基于贻贝类儿茶酚胺聚合物（聚多巴胺，PDA）层的药物负载介孔硅纳米粒子（MSNs）的界面自涂覆策略，用于控制药物释放。当界面 PDA 涂覆的 MSNs 被包封在电纺聚（L-丙交酯）（PLLA）纤维中时，位于界面层内外的药物释放速率可以得到精细控制，在没有界面相互作用的情况下，具有 30 天的短期抗炎布洛芬（IBU）释放，在存在界面相互作用的情况下，具有 90 天的持续长期释放阿霉素（DOX）以抑制潜在的肿瘤复发。进一步发现，DOX@MSN-PDA/IBU/PLLA 杂化纤维支架抑制炎性巨噬细胞和癌细胞的增殖，同时在不同释放阶段支持正常基质成纤维细胞的粘附和增殖。这些结果表明，有机/无机相的界面阻碍层能够以可编程的方式控制界面层内外（缓慢）药物的释放（快速）。我们相信这种界面聚合物策略将在需要时间控制的多药物输送的情况下得到应用。
