Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
Int J Oncol. 2012 Dec;41(6):2260-8. doi: 10.3892/ijo.2012.1636. Epub 2012 Sep 21.
Pancreatic cancer is the fourth largest cause of cancer deaths in the Unites States and the prognosis is grim with <5% survival chances upon diagnosis. The objective of this study was to assess the combined chemopreventive effect of solid lipid nanoparticle (SLN) encapsulated drugs aspirin (ASP), curcumin (CUR) and free sulforaphane (SFN) for the chemoprevention of pancreatic cancer. Experiments were carried out (1) to evaluate the feasibility of encapsulation of these chemopreventive agents within solid lipid systems and (2) to measure the synergistic effects of a combination of ASP with CUR in SLNs mixed with free SFN against cell proliferation and apoptosis in pancreatic cancer cells, MIA PaCa-2 and Panc-1. The SLNs were prepared using a modified solvent evaporation technique and were characterized for particle sizing, encapsulation efficiency and drug release. ASP and CUR SLNs were formulated within the particle size range of 150‑250 nm and were found to have an encapsulation efficiency of 85 and 69%, respectively. Sustained release of drugs over a 96 h period from SLNs was observed. The SLNs were stable over a 3-month storage period at room temperature. Cell viability studies demonstrated that combinations of low doses of ASP SLN (25 µM), CUR SLN (2.5 µM) and free SFN (5 µM) significantly reduced cell viability by 43.6 and 48.49% in MIAPaca-2 and Panc-1 cell lines, respectively. Furthermore, increased apoptosis of 61.3 and 60.37% was found in MIA Paca-2 and Panc-1 cell lines, respectively, in comparison to the individual doses administered. Synergistic effects were demonstrated using MTS and apoptosis assays. Thus, this study successfully demonstrated the feasibility of using a solid lipid nanoparticulate system for the first time to deliver this novel combination chemoprevention regimen, providing valuable evidence for the usability of nanotechnology-based drug regimens towards pancreatic cancer chemoprevention.
胰腺癌是美国第四大癌症死因，预后极差，诊断时的生存率<5%。本研究的目的是评估固体脂质纳米粒（SLN）包封药物阿司匹林（ASP）、姜黄素（CUR）和游离萝卜硫素（SFN）联合化疗预防胰腺癌的效果。实验进行了：（1）评估这些化学预防剂在固体脂质系统中包封的可行性，（2）测量 ASP 与 CUR 在 SLN 中混合游离 SFN 对胰腺癌细胞增殖和凋亡的协同作用，MIA PaCa-2 和 Panc-1。SLN 采用改良溶剂蒸发技术制备，并对粒径、包封效率和药物释放进行了表征。ASP 和 CUR SLN 的粒径范围为 150-250nm，包封效率分别为 85%和 69%。观察到药物在 96 小时内持续释放。SLN 在室温下储存 3 个月仍稳定。细胞活力研究表明，低剂量 ASP SLN（25µM）、CUR SLN（2.5µM）和游离 SFN（5µM）的组合分别使 MIA PaCa-2 和 Panc-1 细胞系的细胞活力降低 43.6%和 48.49%。此外，与单独给药相比，MIA Paca-2 和 Panc-1 细胞系的凋亡分别增加了 61.3%和 60.37%。MTT 和凋亡测定显示协同作用。因此，本研究首次成功证明了使用固体脂质纳米颗粒系统递送这种新型联合化疗预防方案的可行性，为基于纳米技术的药物方案在胰腺癌化学预防中的应用提供了有价值的证据。
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