氯雷他定纳米制剂及其联合用于胰腺癌化学预防的疗效和药代动力学考虑。
Efficacy and Pharmacokinetic Considerations of Loratadine Nanoformulations and its Combinations for Pancreatic Cancer Chemoprevention.
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, California, 91766, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, Marshall B. Ketchum University, Fullerton, California, 92831, USA.
出版信息
Pharm Res. 2020 Jan 2;37(2):21. doi: 10.1007/s11095-019-2737-x.
PURPOSE
Pancreatic cancer (PC) is predicted to become the second leading cause of cancer associated deaths by 2020. Earlier, we confirmed the development and efficacy of our novel Loratadine Self-Microemulsifying-Drug-Delivery-System - Sulforaphane (LOR SMEDDS -SFN) nanoformulation in PC chemoprevention. In this report, we extend our studies to evaluate the PC chemoprevention efficacy of LOR SMEDDS - SFN.
METHODS
The nanoformulation was subjected to in vitro colony formation assays, in vivo oral pharmacokinetics and stability studies.
RESULTS
The colony formation assay using Panc-1 PC cells demonstrated a survival fraction of 0.74 with LOR-SFN (p < 0.001) which further reduced to 0.35 with LOR SMEDDS-SFN treatment (p < 0.0001) confirming the synergistic chemoprevention efficacy of the nanoformulation. Further, the oral pharmacokinetic studies of LOR SMEDDS-SFN showed 4-fold and 9-fold increase in C (503.2 ± 5.8 ng/mL) and oral bioavailability (20,274.8 ± 3711.0 ng·h/mL) for LOR compared to LOR-SFN combination respectively assuring the enhanced performance by the SMEDDS. Additionally, the formulation exhibited statistically non-significant alteration in globule size, zeta potential, drug content and in vitro drug release during stability studies confirming its stability and pharmaceutical acceptability.
CONCLUSION
Our studies have demonstrated a potential of LOR SMEDDS-SFN nanoformulation as an effective PC chemoprevention strategy.
目的
预计到 2020 年，胰腺癌（PC）将成为癌症相关死亡的第二大主要原因。早些时候，我们证实了我们新型的氯雷他定自微乳给药系统-萝卜硫素（LOR SMEDDS-SFN）纳米制剂在 PC 化学预防中的开发和疗效。在本报告中，我们将研究扩展到评估 LOR SMEDDS-SFN 的 PC 化学预防功效。
方法
该纳米制剂进行了体外集落形成测定、体内口服药代动力学和稳定性研究。
结果
使用 Panc-1 PC 细胞进行的集落形成测定显示，LOR-SFN 的存活分数为 0.74（p<0.001），而 LOR SMEDDS-SFN 处理后进一步降低至 0.35（p<0.0001），证实了纳米制剂的协同化学预防功效。此外，LOR SMEDDS-SFN 的口服药代动力学研究显示，LOR 的 C（503.2±5.8ng/mL）和口服生物利用度（20,274.8±3711.0ng·h/mL）分别增加了 4 倍和 9 倍，与 LOR-SFN 组合相比，这确保了 SMEDDS 的增强性能。此外，该制剂在稳定性研究中表现出统计学上无显著变化的粒径、Zeta 电位、药物含量和体外药物释放，证实其稳定性和药物可接受性。
结论
我们的研究表明，LOR SMEDDS-SFN 纳米制剂具有作为有效的 PC 化学预防策略的潜力。
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