Tauchi Yoshihiko, Chono Sumio, Morimoto Kazuhiro
Department of Pharmaceutics, Hokkaido College of Pharmacy, Otaru-city, Japan.
J Drug Target. 2003 Apr;11(3):163-8. doi: 10.1080/10611860310001595247.
To evaluate the utility of a dexamethasone palmitate (DP)-low density lipoprotein (LDL) complex to transport drug into foam cells, the cellular uptake of DP-LDL complex by macrophages and foam cells was examined. The DP-LDL complex was prepared by incubation with DP and LDL, and the DP-LDL complex and murine macrophages were incubated. No cellular uptake of the DP-LDL complex by macrophages was found until 6 h after the start of incubation, but this gradually increased from 12 to 48 h. On the other hand, the cellular uptake of the oxidized DP-LDL complex was already apparent at 3 h after the start incubation, and then markedly increased until 48 h incubation along with that of the lipid emulsion (LE) containing DP (DP-LE). The cellular uptake of DP-LE by foam cells was significantly lower than that by macrophages. However, the cellular uptake of DP-LDL complex by foam cells was similar to that by macrophages. These findings suggest that the DP-LDL complex is oxidatively modified, and then incorporated into macrophages and foam cells through the scavenger receptor pathway. Since selective delivery of drugs into foam cells in the early stage of atherosclerosis is a useful protocol for antiatherosclerosis treatment, the DP-LDL complex appears to be a potentially useful drug-carrier complex for future antiatherosclerotic therapy.
为了评估棕榈酸地塞米松（DP）-低密度脂蛋白（LDL）复合物将药物转运至泡沫细胞中的效用，研究了巨噬细胞和泡沫细胞对DP-LDL复合物的细胞摄取情况。通过将DP与LDL孵育制备DP-LDL复合物，并将DP-LDL复合物与小鼠巨噬细胞一起孵育。在孵育开始后6小时内未发现巨噬细胞对DP-LDL复合物的细胞摄取，但从12小时到48小时逐渐增加。另一方面，氧化型DP-LDL复合物的细胞摄取在孵育开始后3小时就已明显，然后在48小时孵育期间与含DP的脂质乳剂（LE）（DP-LE）一起显著增加。泡沫细胞对DP-LE的细胞摄取显著低于巨噬细胞。然而，泡沫细胞对DP-LDL复合物的细胞摄取与巨噬细胞相似。这些发现表明DP-LDL复合物被氧化修饰，然后通过清道夫受体途径被巨噬细胞和泡沫细胞摄取。由于在动脉粥样硬化早期将药物选择性递送至泡沫细胞是抗动脉粥样硬化治疗的一种有用方案，DP-LDL复合物似乎是未来抗动脉粥样硬化治疗中一种潜在有用的药物载体复合物。
