Meilander N J, Yu X, Ziats N P, Bellamkonda R V
Biomaterials, Cell and Tissue Engineering Laboratory, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106-7207, USA.
J Control Release. 2001 Mar 12;71(1):141-52. doi: 10.1016/s0168-3659(01)00214-0.
Lipid microtubules that self-assemble from a diacetylenic lipid are suitable structures for the sustained release of bioactive agents. Microtubules were loaded with agents under aqueous conditions and embedded in an agarose hydrogel for localization at areas of interest. Protein release from our microtubule-hydrogel delivery system was characterized in vitro, and in vivo biocompatibility was examined. The influences of protein molecular weight and initial loading concentration on release profile were evaluated by releasing test proteins myoglobin, albumin, and thyroglobulin. Protein molecular weight inversely affected the release rate, and loading with a higher protein concentration increased the mass but not the percent of initially loaded protein released daily. Preservation of protein activity was demonstrated by the ability of a neurotrophic factor released from the delivery system to induce neurite extension in PC12 cells. Bovine aortic smooth muscle cells co-cultured with the microtubule-hydrogel system showed no evidence of cytotoxicity and proliferated in the presence of the microtubules. Subcutaneous implantation of microtubules in rodents revealed no significant inflammatory response after 10 days. Our microtubule-hydrogel system is useful for applications where sustained release without contact between agent and organic solvents is desired.
由二乙炔脂质自组装形成的脂质微管是用于生物活性剂持续释放的合适结构。在水性条件下将微管用试剂加载，并嵌入琼脂糖水凝胶中以定位在感兴趣的区域。对我们的微管-水凝胶递送系统中的蛋白质释放进行了体外表征，并检测了体内生物相容性。通过释放测试蛋白肌红蛋白、白蛋白和甲状腺球蛋白，评估了蛋白质分子量和初始加载浓度对释放曲线的影响。蛋白质分子量对释放速率有反向影响，加载更高的蛋白质浓度会增加每日释放的初始加载蛋白质的质量，但不会增加其百分比。从递送系统释放的神经营养因子诱导PC12细胞中神经突延伸的能力证明了蛋白质活性的保留。与微管-水凝胶系统共培养的牛主动脉平滑肌细胞没有细胞毒性的迹象，并且在微管存在的情况下增殖。在啮齿动物中皮下植入微管10天后未发现明显的炎症反应。我们的微管-水凝胶系统可用于需要在试剂与有机溶剂不接触的情况下持续释放的应用。
