a Department of Pharmaceutics , Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University) , Bilaspur (C.G.) , India.
Artif Cells Nanomed Biotechnol. 2018 Sep;46(6):1236-1247. doi: 10.1080/21691401.2017.1366338. Epub 2017 Aug 29.
Colorectal cancer (CRC) ranked second in females and third in males among all type of cancers diagnosed. About 1.4 million cases took place with 693,900 deaths in 2012. It can occur either in colon or rectum. Thus, we aimed to develop and optimize oxaliplatin (OP) loaded solid lipid nanoparticles (SLNs).
SLNs containing tristearin, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), Lipoid S75, and Tween 80 was developed. Box-Behnken design was applied for optimization of SLNs and optimized formulation was selected for conjugation with folic acid (FA). Optimized formulations were evaluated for various physiochemical parameters viz., particle size (PS), zeta potential, %entrapment efficiency (EE), morphology, X-ray diffraction (XRD), and differential scanning calorimetry (DSC).
OP loaded uncoupled SLNs (OPSLNs) and OP loaded FA coupled SLNs (OPSLNFs) formulations revealed good EE, 49.2 ± 0.38% and 43.5 ± 0.59%, respectively and small PS, 146.2 ± 4.4 nm, and 158.8 ± 5.6 nm, respectively. XRD pattern and DSC results confirmed that OP was uniformly distributed in amorphous form within SLNs. In vitro drug release study of OPSLNs and OPSLNFs formulation revealed sustained drug release pattern of OP for up to 6 d. Anticancer activity on HT-29 cell line indicated the highest potency of OPSLNFs as compared to OPSLNs and OP solution.
The present work illustrated the higher sensitivity of HT-29 cells to the drug entrapped in OPSLNFs as compared to OPSLNs and OP solution. Hence, this novel strategy might be a promising approach for the management of CRC.
在 2012 年诊断出的所有癌症类型中，结直肠癌（CRC）在女性中排名第二，在男性中排名第三。当年发生了约 140 万例病例，有 693900 人死亡。它可以发生在结肠或直肠。因此，我们旨在开发和优化载奥沙利铂（OP）的固体脂质纳米粒（SLNs）。
开发了含有三硬脂精、1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺（DSPE）、Lipoid S75 和 Tween 80 的 SLNs。采用 Box-Behnken 设计对 SLNs 进行优化，并选择优化的配方与叶酸（FA）偶联。对优化的配方进行了各种物理化学参数的评估，如粒径（PS）、Zeta 电位、包封效率（EE）、形态、X 射线衍射（XRD）和差示扫描量热法（DSC）。
载 OP 的未偶联 SLNs（OPSLNs）和载 OP 的 FA 偶联 SLNs（OPSLNFs）制剂显示出良好的 EE，分别为 49.2±0.38%和 43.5±0.59%，以及较小的 PS，分别为 146.2±4.4nm 和 158.8±5.6nm。XRD 图谱和 DSC 结果证实，OP 均匀分布在 SLNs 中呈无定形状态。OPSLNs 和 OPSLNFs 制剂的体外药物释放研究表明，OP 可在 6 天内持续释放药物。在 HT-29 细胞系上的抗癌活性表明，与 OPSLNs 和 OP 溶液相比，OPSLNFs 的药效最强。
本工作表明，HT-29 细胞对 OPSLNFs 中包封的药物的敏感性高于 OPSLNs 和 OP 溶液。因此，这种新策略可能是结直肠癌治疗的一种有前途的方法。
