Rivero Berti Ignacio, Rodenak-Kladniew Boris E, Katz Sergio F, Arrua Eva Carolina, Alvarez Vera A, Duran Nelson, Castro Guillermo R
Laboratorio de Nanobiomateriale, CINDEFI, Departamento de Química, Facultad de Ciencias Exactas, CONICET (CCT La Plata), Universidad Nacional de La Plata (UNLP), La Plata, Argentina.
Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, CCT-La Plata, Facultad de Ciencias Médicas, La Plata, Argentina.
Front Chem. 2022 Jul 7;10:914126. doi: 10.3389/fchem.2022.914126. eCollection 2022.
Violacein (Viol) is a bacterial purple water-insoluble pigment synthesized by and other microorganisms that display many beneficial therapeutic properties including anticancer activity. Viol was produced, purified in our laboratory, and encapsulated in a nanostructured lipid carrier (NLC). The NLC is composed of the solid lipid myristyl myristate, an oily lipid mixture composed of capric and caprylic acids, and the surfactant poloxamer P188. Dormant lipase from was incorporated into the NLC-Viol to develop an active release system. The NLC particle size determined by dynamic light scattering brings around 150 nm particle size and ≈ -9.0 mV with or without lipase, but the incorporation of lipase increase the PdI from 0.241 to 0.319 (≈32%). For scaffold development, a 2.5 hydroxypropyl methylcellulose/chitosan ratio was obtained after optimization of a composite for extrusion in a 3D-bioprinter developed and constructed in our laboratory. Final Viol encapsulation efficiency in the printings was over 90%. Kinetic release of the biodye at pH = 7.4 from the mesh containing NLC-lipase showed roughly 20% Viol fast release than without the enzyme. However, both Viol kinetic releases displayed similar profiles at pH = 5.0, where the lipase is inactive. The kinetic release of Viol from the NLC-matrices was modeled and the best correlation was found with the Korsmeyer-Peppas model (R = 0.95) with < 0.5 suggesting a Fickian release of Viol from the matrices. Scanning Electron Microscope (SEM) images of the NLC-meshes showed significant differences before and after Viol's release. Also, the presence of lipase dramatically increased the gaps in the interchain mesh. XRD and Fourier Transform Infrared (FTIR) analyses of the NLC-meshes showed a decrease in the crystalline structure of the composites with the incorporation of the NLC, and the decrease of myristyl myristate in the mesh can be attributed to the lipase activity. TGA profiles of the NLC-meshes showed high thermal stability than the individual components. Cytotoxic studies in A549 and HCT-116 cancer cell lines revealed high anticancer activity of the matrix mediated by mucoadhesive chitosan, plus the biological synergistic activities of violacein and lipase.
紫菌素（Viol）是一种由 及其他微生物合成的细菌紫色水不溶性色素，具有许多有益的治疗特性，包括抗癌活性。紫菌素在我们实验室中制备、纯化，并封装在纳米结构脂质载体（NLC）中。NLC由固体脂质肉豆蔻酸肉豆蔻酯、由癸酸和辛酸组成的油性脂质混合物以及表面活性剂泊洛沙姆P188构成。将来自 的休眠脂肪酶掺入NLC-紫菌素中以开发一种活性释放系统。通过动态光散射测定的NLC粒径，无论有无脂肪酶，粒径均约为150 nm，ζ电位约为-9.0 mV，但掺入脂肪酶会使多分散指数（PdI）从0.241增加到0.319（约32%）。为了进行支架开发，在对我们实验室开发和构建的用于3D生物打印机挤出的复合材料进行优化后，得到了2.5的羟丙基甲基纤维素/壳聚糖比例。打印物中紫菌素的最终包封效率超过90%。在pH = 7.4时，含有NLC-脂肪酶的网状物中生物染料紫菌素的动力学释放显示，与不含该酶的情况相比，紫菌素的快速释放率约高20%。然而，在pH = 5.0时，两种紫菌素的动力学释放显示出相似的曲线，此时脂肪酶无活性。对紫菌素从NLC基质中的动力学释放进行了建模，发现与Korsmeyer-Peppas模型（R = 0.95）的相关性最佳，n < 0.5表明紫菌素从基质中呈菲克扩散释放。NLC网状物的扫描电子显微镜（SEM）图像显示紫菌素释放前后存在显著差异。此外，脂肪酶的存在显著增加了链间网状结构中的间隙。NLC网状物的X射线衍射（XRD）和傅里叶变换红外光谱（FTIR）分析表明，随着NLC的掺入，复合材料的晶体结构减少，网状物中肉豆蔻酸肉豆蔻酯的减少可归因于脂肪酶的活性。NLC网状物的热重分析（TGA）曲线显示其热稳定性高于各个组分。对A549和HCT-116癌细胞系的细胞毒性研究表明，由黏附性壳聚糖介导的基质具有高抗癌活性，以及紫菌素和脂肪酶的生物协同活性。
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