Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea; Department of Biological Science, Korea University, Seoul 136-701, Republic of Korea.
Small. 2013 Oct 25;9(20):3468-76. doi: 10.1002/smll.201300427. Epub 2013 Apr 15.
An optimized electrodropping system produces homogeneous core-shell microcapsules (C-S MCs) by using poly(L-lactic-co-glycolic acid) (PLGA) and alginate. Fluorescence imaging clearly shows the C-S domain in the MC. For release control, the use of high-molecular-weight PLGA (HMW 270 000) restrains the initial burst release of protein compared to that of low-MW PLGA (LMW 40 000). Layer-by-layer (LBL) assembly of chitosan and alginate on MCs is also useful in controlling the release profile of biomolecules. LBL (7-layer) treatment is effective in suppressing the initial burst release of protein compared to no LBL (0-layer). The difference of cumulative albumin release between HMW (7-layer LBL) and LMW (0-layer LBL) PLGA is determined to be more than 40% on day 5. When dual angiogenic growth factors (GFs), such as platelet-derived GF (PDGF) and vascular endothelial GF (VEGF), are encapsulated separately in the core and shell domains, respectively, the VEGF release rate is much greater than that of PDGF, and the difference of the cumulative release percentage between the two GFs is about 30% on day 7 with LMW core PLGA and more than 45% with HMW core PLGA. As for the angiogenic potential of MC GFs with human umbilical vein endothelial cells (HUVECs), the fluorescence signal of CD31+ suggests that the angiogenic sprout of ECs is more active in MC-mediated GF delivery than conventional GF delivery, and this difference is significant, based on the number of capillary branches in the unit area. This study demonstrates that the fabrication of biocompatible C-S MCs is possible, and that the release control of biomolecules is adjustable. Furthermore, MC-mediated GFs remain in an active form and can upregulate the angiogenic activity of ECs.
优化的电喷系统使用聚（L-丙交酯-共-乙交酯）（PLGA）和海藻酸钠产生均匀的核壳微胶囊（C-S MCs）。荧光成像清楚地显示了 MC 中的 C-S 域。为了控制释放，与低分子量 PLGA（LMW 40000）相比，使用高分子量 PLGA（HMW 270000）可抑制蛋白质的初始突释。在 MC 上进行壳聚糖和海藻酸钠的层层（LBL）组装也有助于控制生物分子的释放曲线。与无 LBL（0 层）相比，LBL（7 层）处理在抑制蛋白质的初始突释方面非常有效。在第 5 天，HMW（7 层 LBL）和 LMW（0 层 LBL）PLGA 之间白蛋白累积释放的差异确定为超过 40%。当将血小板衍生生长因子（PDGF）和血管内皮生长因子（VEGF）等双重血管生成生长因子（GFs）分别包封在核和壳域中时，VEGF 的释放速率远大于 PDGF，并且在第 7 天，两种 GFs 的累积释放百分比差异约为 30%，LMW 核 PLGA 超过 45%，HMW 核 PLGA。对于具有人脐静脉内皮细胞（HUVEC）的 MC GFs 的血管生成潜力，CD31+的荧光信号表明，在 MC 介导的 GF 递送中，EC 的血管生成芽比传统 GF 递送更活跃，这种差异基于单位面积中的毛细血管分支数是显著的。这项研究表明，制造生物相容性的 C-S MCs 是可能的，并且生物分子的释放控制是可调节的。此外，MC 介导的 GFs 保持在活性形式，并可以上调 EC 的血管生成活性。
