载有核糖昔的纳米脂质载体靶向乳腺癌的制剂优化、特性衰减及研究。

Ribociclib Nanostructured Lipid Carrier Aimed for Breast Cancer: Formulation Optimization, Attenuating Specification, and Scrutinization.

机构信息

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.

Nanobiotech Lab, Kirori Mal College, University of Delhi, Delhi 110007, India.

出版信息

Biomed Res Int. 2022 Feb 3;2022:6009309. doi: 10.1155/2022/6009309. eCollection 2022.

PURPOSE

The current investigation is on the explicit development and evaluation of nanostructured lipidic carriers (NLCs) through the oral route to overcome the inherent lacuna of chemotherapeutic drug, in which Ribociclib (RBO) was used for breast cancer to diminish the bioavailability issue.

METHOD

The RBO-NLCs were prepared using the solvent evaporation method and optimized method by the Box-Behnken design (BBD). Various assessment parameters characterized the optimized formulation and their study.

RESULTS

The prepared NLCs exhibited mean particle size of 114.23 ± 2.75 nm, mean polydispersity index of 0.649 ± 0.043, and high entrapment efficiency of 87.7 ± 1.79%. The structural analysis by TEM revealed the spherical size of NLCs and uniform drug distribution. An drug release study was established through the 0.1 N HCl pH 1.2, acetate buffer pH 4.5, and phosphate buffer pH 6.8 with % cumulative drug release of 86.71 ± 8.14, 85.82 ± 4.58, and 70.98 ± 5.69%, was found respectively, compared with the RBO suspension (RBO-SUS). intestinal gut permeation studies unveiled a 1.95-fold gain in gut permeation by RBO-NLCs compared with RBO-SUS. lipolysis suggests the drug availability at the absorption site. haemolysis study suggests the compatibility of NLCs to red blood cells compared to the suspension of the pure drug. The confocal study revealed the depth of penetration of the drug into the intestine by RBO-NLCs which was enhanced compared to RBO-SUS. A cell line study was done in MCF-7 and significantly reduced the IC value compared to the pure drug. The parameters suggested the enhanced bioavailability by 3.54 times of RBO-NLCs as compared to RBO-SUS.

CONCLUSION

The , ex vivo, and results showed a prominent potential for bioavailability enhancement of RBO and effective breast cancer therapy.

目的

本研究旨在通过口服途径开发和评估纳米结构脂质载体（NLCs），以克服化疗药物固有的缺陷，其中利波昔布（RBO）被用于乳腺癌以减少生物利用度问题。

方法

采用溶剂蒸发法制备 RBO-NLCs，并采用 Box-Behnken 设计（BBD）优化方法。对优化后的配方及其研究进行了各种评价参数的表征。

结果

所制备的 NLCs 粒径为 114.23 ± 2.75nm，平均多分散指数为 0.649 ± 0.043，包封率为 87.7 ± 1.79%。TEM 结构分析显示 NLCs 呈球形且药物分布均匀。通过 0.1N HCl pH 1.2、醋酸盐缓冲液 pH 4.5 和磷酸盐缓冲液 pH 6.8 进行药物释放研究，发现 RBO-NLCs 的累积药物释放率分别为 86.71 ± 8.14%、85.82 ± 4.58%和 70.98 ± 5.69%，与 RBO 混悬剂（RBO-SUS）相比。肠道渗透研究表明，与 RBO-SUS 相比，RBO-NLCs 使肠道渗透增加了 1.95 倍。脂肪酶提示吸收部位的药物可用性。溶血研究表明，与纯药物混悬剂相比，NLCs 与红细胞具有更好的相容性。共聚焦研究显示，与 RBO-SUS 相比，RBO-NLCs 使药物更深地渗透到肠道中。细胞系研究表明，与纯药物相比，RBO-NLCs 显著降低了 IC 值。这些参数表明，与 RBO-SUS 相比，RBO-NLCs 的生物利用度提高了 3.54 倍。