Architectural layer-by-layer assembly of drug nanocapsules with PEGylated polyelectrolytes.
Architectural layer-by-layer assembly of drug nanocapsules with PEGylated polyelectrolytes.
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DOI：
10.1039/c2sm25683e
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发表时间：
2012-01-01
期刊：
影响因子：
3.4
通讯作者：
Lvov YM
中科院分区：
文献类型：
--
作者：
Shutava TG;Pattekari PP;Arapov KA;Torchilin VP;Lvov YM
在含有不带电荷稳定剂的溶液中，将紫杉醇和喜树碱等难溶药物层层组装到药物纳米芯上，制备了直径150~200 nm的胶囊，其中含有60~70wt%的难溶药物紫杉醇和喜树碱。胶囊外壳结构和厚度的优化允许浓缩(3-5毫克/毫升)胶体在等渗盐缓冲液中稳定。通过在每个双层构建步骤中使用低分子量聚氨基酸(聚L赖氨酸和聚L谷氨酸)与聚乙二醇、肝素和牛血清白蛋白相结合的嵌段共聚物来防止纳米粒子在免洗涤液晶组装过程中的聚集。在这个免清洗的LBL过程中，使用了最少量的聚电解质来为纳米颗粒表面充电。这种聚乙二醇化的壳层使药物纳米胶囊在PBS缓冲液中具有很高的胶体稳定性，并增加了蛋白质的粘附性。通过动态光散射、凝胶迁移率测量、紫外-可见光谱、透射电子显微镜、扫描电子显微镜和激光共聚焦显微镜成像等手段，对无水洗LBL聚电解质纳米胶囊的组装过程、胶体稳定性和纳米粒子形态进行了监测。
150–200 nm diameter capsules containing 60–70 wt % of poorly soluble drugs, paclitaxel and camptothecin, were produced by layer-by-layer (LbL) assembly on drug nanocores in a solution containing uncharged stabilizers. Optimization of capsule shell architecture and thickness allowed for concentrated (3–5 mg/mL) colloids that are stable in isotonic salt buffers. Nanoparticle aggregation during the washless LbL-assembly was prevented by using low molecular weight block-copolymers of poly(amino acids) (poly-L-lysine and poly-L-glutamic acid) with polyethylene glycol (PEG) in combination with heparin and bovine serum albumin at every bilayer building step. Minimal amounts of the polyelectrolytes were used to recharge the surface of nanoparticles in this non-washing LbL process. Such PEGylated shells resulted in drug nanocapsules with high colloidal stability in PBS buffer and increased protein adhesion resistance. The washless LbL polyelectrolyte nanocapsule assembly process, colloidal stability and nanoparticle morphology were monitored by dynamic light scattering and electrophoretic mobility measurements, UV-vis spectroscopy, TEM, SEM and laser confocal microscopy imaging.