Veerla Sarath Chandra, Kim Da Reum, Yang Sung Yun
Department of Organic Materials Engineering, Chungnam National University, 99, Daehak-ro, Yuseong-gu, Daejeon, 34134 Korea.
Biomater Res. 2018 Mar 13;22:7. doi: 10.1186/s40824-018-0119-9. eCollection 2018.
Controlled drug delivery system is highly important for not only prolonged the efficacy of drug but also cellular development for tissue engineering. A number of biopolymer composites and nanostructured carriers behave been used for the controlled drug delivery of therapeutics. Recently, in vitro microfluidic devices that mimic the human body have been developed for drug-delivery applications.
A microfluidic channel was fabricated via a two-step process: (i) polydimethyl siloxane (PDMS) and curing agent were poured with a 10:2 mass ratio onto an acrylic mold with two steel pipes, and (ii) calcium alginate beads were synthesized using sodium alginate and calcium chloride solutions. Different amounts (10, 25, 50 μg) of graphene oxide (GO) were then added by Hummers method, and studies on the encapsulation and release of the model drug, risedronate (Ris), were performed using control hydrogel beads (pH 6.3), GO-containing beads (10GO, 25GO and 50GO), and different pH conditions. MC3T3 osteoblastic cells were cultured in a microchannel with Ris-loaded GO-hydrogel beads, and their proliferation, viability, attachment and spreading were assessed for a week.
The spongy and textured morphology of pristine hydrogel beads was converted to flowery and rod-shaped structures in drug-loaded hydrogel beads at reduced pH (6.3) and at a lower concentration (10 μg) of GO. These latter 10GO drug-loaded beads rapidly released their cargo owing to the calcium phosphate deposited on the surface. Notably, beads containing a higher amount of GO (50GO) exhibited an extended drug-release profile. We further found that MC3T3 cells proliferated continuously in vitro in the microfluidic channel containing the GO-hydrogel system. MTT and live/dead assays showed similar proliferative potential of MC3T3 cells. Therefore, a microfluidic device with microchannels containing hydrogel beads formulated with different amounts of GO and tested under various pH conditions could be a promising system for controlled drug release.
The GO and drug (risedronate, Rig) were directed loaded into a hydrogel placed in a microchannel. Through interactions such as hydrogen bonding between Go and the Rig-loaded GO-hydrogel beads, the bead-loaded microfluidic device supported MC3T3 proliferation and development as osteoblast without additional osteogenic differentiation supplements.
可控药物递送系统不仅对于延长药物疗效非常重要，而且对于组织工程的细胞发育也至关重要。许多生物聚合物复合材料和纳米结构载体已被用于治疗药物的可控递送。最近，已开发出模拟人体的体外微流控装置用于药物递送应用。
通过两步法制造微流控通道：（i）将聚二甲基硅氧烷（PDMS）和固化剂按质量比10:2倒入带有两根钢管的丙烯酸模具中，（ii）使用海藻酸钠和氯化钙溶液合成海藻酸钙珠。然后通过Hummers法添加不同量（10、25、50μg）的氧化石墨烯（GO），并使用对照水凝胶珠（pH 6.3）、含GO的珠（10GO、25GO和50GO）以及不同pH条件对模型药物利塞膦酸盐（Ris）的包封和释放进行研究。将MC3T3成骨细胞在装有载有Ris的GO-水凝胶珠的微通道中培养，并评估其增殖、活力、附着和铺展情况，为期一周。
在pH降低（6.3）且GO浓度较低（10μg）时，原始水凝胶珠的海绵状和有纹理的形态在载药的水凝胶珠中转变为花状和棒状结构。由于表面沉积有磷酸钙，这些载有10GO的药物珠迅速释放其货物。值得注意的是，含有较高量GO（50GO）的珠表现出延长的药物释放曲线。我们进一步发现，MC3T3细胞在含有GO-水凝胶系统的微流控通道中在体外持续增殖。MTT和活/死检测显示MC3T3细胞具有相似的增殖潜力。因此，一种具有包含用不同量GO配制的水凝胶珠并在各种pH条件下进行测试的微通道的微流控装置可能是一种有前途的可控药物释放系统。
将GO和药物（利塞膦酸盐，Rig）直接负载到置于微通道中的水凝胶中。通过GO与载有Rig的GO-水凝胶珠之间的氢键等相互作用，装有珠的微流控装置支持MC3T3作为成骨细胞的增殖和发育，而无需额外的成骨分化补充剂。
