University of Ljubljana, Faculty of Pharmacy, Askerceva 7, Ljubljana, Slovenia.
Int J Pharm. 2010 May 5;390(1):61-9. doi: 10.1016/j.ijpharm.2009.10.011. Epub 2009 Oct 13.
The potential for colloidal carriers to increase drug bioavailability has spurred a renewed interest in their uptake mechanisms and movement within cells. Solid lipid nanoparticles (SLN) were used as a carrier for a promising chemopreventive drug, resveratrol (RSV). The effects of SLN, empty or loaded with RSV (SLN-RSV), on the internalization, growth, morphology, metabolic activity and genetic material of keratinocytes were compared to those of RSV in solution. Fluorescence images clearly showed that SLN with a size below 180 nm move promptly through the cell membrane, distribute throughout the cytosol, move successively among different cellular levels and localize in the perinuclear region without inducing cytotoxicity. RSV solubility, stability and intracellular delivery were all increased by loading into SLN. The release profile of RSV showed a biphasic pattern, reflecting its distribution in SLN. RSV in solution was slightly cytotoxic. That was prevented by loading it into solid lipid nanoparticles, which preserved cell morphology. The cytostatic effect of SLN-RSV was much more expressed than that of RSV in solution. Delivery of RSV by SLN contributes to effectiveness of RSV on decreasing cell proliferation, with potential benefits for prevention of skin cancer.
胶态载体提高药物生物利用度的潜力促使人们重新关注其摄取机制和在细胞内的运动。固体脂质纳米粒（SLN）被用作一种有前途的化学预防药物白藜芦醇（RSV）的载体。将 SLN（空白或负载 RSV 的 SLN[SLN-RSV]）与溶液中的 RSV 相比，比较它们对角质形成细胞的内化、生长、形态、代谢活性和遗传物质的影响。荧光图像清楚地表明，尺寸小于 180nm 的 SLN 迅速穿过细胞膜，分布在整个细胞质中，在不同的细胞水平之间依次移动，并定位于核周区，而不会引起细胞毒性。将 RSV 载入 SLN 提高了 RSV 的溶解度、稳定性和细胞内传递。RSV 的释放曲线呈两相模式，反映了其在 SLN 中的分布。溶液中的 RSV 略有细胞毒性。通过将其载入固体脂质纳米粒可以防止这种情况，同时保持细胞形态。与溶液中的 RSV 相比，SLN-RSV 的细胞生长抑制作用更为明显。SLN 递送 RSV 有助于 RSV 降低细胞增殖的有效性，为预防皮肤癌带来潜在益处。
