Grijalvo Santiago, Alagia Adele, Puras Gustavo, Zárate Jon, Mayr Judith, Pedraz José Luis, Eritja Ramon, Díaz David Díaz
Institute of Organic Chemistry, University of Rgensburg, Universitätstrasse 31, 93040 Regensburg, Germany.
J Mater Chem B. 2017 Oct 7;5(37):7756-7767. doi: 10.1039/c7tb01691c. Epub 2017 Sep 18.
Two polysaccharide-based hydrogels made of only κ-carrageenan (4%; w/v) or of a mixture of methylcellulose:κ-carrageenan (2%; w/v) were used to encapsulate cationic nioplexes. These vesicular particles were made of a synthetic aminolipid and polysorbate-80 (Tween-80), as a non-ionic surfactant agent. According to oscillatory rheological measurements, the presence of nioplexes did not compromise the mechanical integrity of the gels. In vitro niosomal release experiments demonstrated the liberation of nioplexes up to 24 h, and the curves were fitted according to Higuchi, Korsmeyer-Peppas and Weibull equation models, which indicated Fickian-diffusion controlled mechanisms. Besides nioplexes, cervical cancer cells were also entrapped within the biohydrogels. Cell release confirmed that these materials did not affect the cell viability, allowing cells to spread and proliferate after 24 h. The applicability of these biocompatible hydrogels was also extended to gene delivery. In this regard, the best silencing activities were found when cationic niosomes were complexed with antisense oligonucleotides in KC hydrogels. Nioplexes were able to release through the hydrogel and promoted silencing of luciferase expression in the presence of serum without using commercially available cationic lipids. Overall, the formation of such hybrid materials by integrating cationic nioplexes within biodegradable hydrogels provides a new perspective for the delivery of macromolecular therapeutics.
两种仅由κ-卡拉胶（4%；w/v）或甲基纤维素与κ-卡拉胶的混合物（2%；w/v）制成的多糖基水凝胶被用于包封阳离子纳米复合物。这些囊泡颗粒由一种合成氨基脂质和聚山梨酯-80（吐温80）制成，聚山梨酯-80作为一种非离子表面活性剂。根据振荡流变学测量，纳米复合物的存在并未损害凝胶的机械完整性。体外脂质体释放实验表明纳米复合物在长达24小时内都有释放，并且根据Higuchi、Korsmeyer-Peppas和Weibull方程模型对曲线进行拟合，结果表明是菲克扩散控制机制。除了纳米复合物外，宫颈癌细胞也被包裹在生物水凝胶中。细胞释放证实这些材料不会影响细胞活力，使细胞在24小时后能够扩散和增殖。这些生物相容性水凝胶的适用性还扩展到了基因递送。在这方面，当阳离子脂质体在κ-卡拉胶水凝胶中与反义寡核苷酸复合时，发现了最佳的沉默活性。纳米复合物能够通过水凝胶释放，并在有血清存在的情况下促进荧光素酶表达的沉默，而无需使用市售的阳离子脂质。总体而言，通过将阳离子纳米复合物整合到可生物降解水凝胶中来形成这种杂化材料，为大分子治疗药物的递送提供了一个新的视角。
