Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, CCT-La Plata, Facultad de Ciencias Médicas, La Plata, Argentina.
Laboratorio de Nanobiomateriales, CINDEFI, Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP) -CONICET (CCT La Plata), Calle 47 y 115, B1900AJI, La Plata, Buenos Aires, Argentina.
Colloids Surf B Biointerfaces. 2021 Jun;202:111710. doi: 10.1016/j.colsurfb.2021.111710. Epub 2021 Mar 19.
The development of versatile carriers to deliver chemotherapeutic agents to specific targets with establishing drug release kinetics and minimum undesirable side effects is becoming a promising relevant tool in the medical field. Magnetic hybrid nanostructured lipid carriers (NLC) were prepared by incorporation of 1,8-cineole (CN, a monoterpene with antiproliferative properties) and maghemite nanoparticles (MNPs) into a hybrid matrix composed of myristyl myristate coated with chitosan. Hybrid NLC characterized by DLS and TEM confirmed the presence of positively charged spherical nanoparticles of around 250 nm diameter and +10.2 mV of Z-potential. CN encapsulation into the lipid core was greater than 75 % and effectively released in 24 h. Modification of the crystalline structure of nanoparticles after incorporation of CN and MNPs was observed by XRD, DSC, and TGA analyses. Superparamagnetic NLC behavior was verified by recording the magnetization using a vibrating scanning magnetometer. NLC resulted in more cytotoxic than free CN in HepG2 and A549 cell lines. Particularly, viability inhibition of HepG2 and A549 cells was increased from 35 % to 55 % and from 38 % to 61 %, respectively, when 8 mM CN was incorporated into the lipid NPs at 24 h. Green fluorescent-labeled NLC with DIOC18 showed an enhanced cellular uptake with chitosan-coated NLC. Besides, no cytotoxicity of the formulations in normal WI-38 cells was observed, suggesting that the developed hybrid NLC system is a safe and good potential candidate for the selective delivery and potentiation of anticancer drugs.
开发多功能载体，将化疗药物递送到特定靶点，建立药物释放动力学和最小的不良副作用，这在医学领域正成为一种有前途的相关工具。通过将 1,8-桉树脑（CN，一种具有抗增殖特性的单萜）和磁赤铁矿纳米颗粒（MNPs）掺入由硬脂酸肉豆蔻酯涂覆壳聚糖组成的混合基质中，制备了多功能磁性混合纳米结构化脂质载体（NLC）。通过 DLS 和 TEM 对混合 NLC 进行了表征，证实了存在带正电荷的直径约为 250nm 的球形纳米颗粒和+10.2mV 的 Zeta 电位。CN 包封在脂质核中大于 75%，并在 24 小时内有效释放。通过 XRD、DSC 和 TGA 分析观察到 CN 和 MNPs 掺入后纳米颗粒的晶体结构发生了变化。通过使用振动扫描磁强计记录磁化强度来验证超顺磁 NLC 的行为。与游离 CN 相比，NLC 在 HepG2 和 A549 细胞系中表现出更高的细胞毒性。特别是，当在脂质 NPs 中掺入 8mM 的 CN 时，HepG2 和 A549 细胞的活力抑制分别从 35%增加到 55%和从 38%增加到 61%。用 DIOC18 标记的绿色荧光 NLC 显示出与壳聚糖涂覆的 NLC 增强的细胞摄取。此外，在正常 WI-38 细胞中未观察到制剂的细胞毒性，这表明所开发的混合 NLC 系统是一种安全且有潜力的候选药物，可用于选择性递药和增强抗癌药物的作用。
