Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion-Israel Institute of Technology, Technion City, Haifa, Israel.
Biomater Sci. 2017 Oct 24;5(11):2295-2309. doi: 10.1039/c7bm00675f.
In this work, we report a new type of poly(vinyl alcohol)-g-poly(N-isopropylacrylamide) (PVA-g-PNiPAAm) amphiphilic nanogel produced by the non-covalent crosslinking of PVA polyol domains in preformed polymeric micelles with boric acid. The nanomaterials showed sizes in the 100-250 nm range (DLS) and a spherical morphology (HR-SEM). We demonstrated that the size of the polymeric micelles could be fine-tuned by changing the concentration (and the aggregation pattern) of the polymeric amphiphile in water. Upon crosslinking, the polymeric micelles turned into physically stable amphiphilic nanogels that displayed both size and size distribution similar to the micellar precursor for up to two weeks, even under disfavored conditions of concentration and temperature that, in the case of non-crosslinked counterparts, resulted in quick disassembly. In addition, we show for the first time the feasibility of spray-drying technology to consolidate the 3D network formed between PVA and boric acid and to produce stable powders that can be reconstituted upon use at any desired concentration. Moreover, the formation of a borated surface conferred the nanogels with good mucoadhesiveness in vitro. Finally, these novel nanomaterials showed optimal cell compatibility in a model of the intestinal epithelium, the Caco2 cell line. Overall results demonstrate the unprecedented versatility of the proposed modular approach and opens completely new horizons in the application of polymeric micelles and other self-assembled polymeric nanomaterials in diagnostics and therapeutics.
在这项工作中，我们报告了一种新型的聚乙烯醇-接枝-聚（N-异丙基丙烯酰胺）（PVA-g-PNiPAAm）两亲性纳米凝胶，它是通过硼酸非共价交联预形成的聚合物胶束中的聚乙烯醇多醇域制备的。纳米材料的粒径在 100-250nm 范围内（DLS），呈球形形态（HR-SEM）。我们证明了通过改变聚合物两亲物在水中的浓度（和聚集模式）可以精细调节聚合物胶束的大小。交联后，聚合物胶束转变成物理稳定的两亲性纳米凝胶，其粒径和粒径分布与胶束前体相似，长达两周，即使在浓度和温度不利的条件下也是如此，对于未交联的对应物，会导致快速解体。此外，我们首次展示了喷雾干燥技术的可行性，以巩固 PVA 和硼酸之间形成的 3D 网络，并生产出在任何所需浓度下都可以重新配制的稳定粉末。此外，硼酸化表面的形成赋予纳米凝胶良好的体外粘膜粘附性。最后，这些新型纳米材料在肠道上皮细胞模型 Caco2 细胞系中表现出最佳的细胞相容性。总体结果证明了所提出的模块化方法前所未有的多功能性，并为聚合物胶束和其他自组装聚合物纳米材料在诊断和治疗中的应用开辟了全新的视野。
