Smeesters C, Giroux L, Vinet B, Arnoux R, Chaland P, Corman J, St-Louis G, Daloze P
Department of Surgery, Hôpital Notre-Dame, Montreal, PQ.
Can J Surg. 1988 Jan;31(1):34-6.
A preparation of cyclosporine (CsA) in liposomes was tested in the rat to evaluate its effectiveness in reducing CsA nephrotoxicity. The drug was injected intravenously in unilaterally nephrectomized Lewis rats at a daily dose of 25 mg/kg for 14 days, either in a cremophore solution (eight rats) or in a preparation of liposomes (eight rats). Another group of four animals received the cremophore solution alone. Overall, rats treated with the CsA-liposome preparation had reduced toxicity, exhibiting better survival rates and less weight loss than those treated with the CsA-cremophore. Incorporating CsA into liposomes induced a statistically significant (p less than 0.05) reduction in the otherwise progressive increase of serum creatinine during week 2 of the experiment. Following administration of CsA-liposome preparation, epithelial cells of the proximal renal tubules appeared morphologically normal, without evidence of vacuolization, which is characteristic of CsA nephrotoxicity and was seen in the CsA-cremophore group. Although the exact mechanism is not clearly understood, it is likely that the tissue distribution of CsA, when incorporated into liposomes, is modified in favour of the reticuloendothelial cells, thereby sparing highly sensitive, but non-target organs such as the kidneys.
对脂质体包裹的环孢素（CsA）制剂在大鼠体内进行了试验，以评估其降低CsA肾毒性的有效性。将该药物以每日25 mg/kg的剂量静脉注射给单侧肾切除的Lewis大鼠，持续14天，一组8只大鼠使用聚氧乙烯蓖麻油溶液中的CsA（环孢素溶液组），另一组8只大鼠使用脂质体制剂包裹的CsA（环孢素脂质体组）。另一组4只动物仅接受聚氧乙烯蓖麻油溶液。总体而言，与环孢素溶液组相比，接受环孢素脂质体制剂治疗的大鼠毒性降低，存活率更高，体重减轻更少。在实验第2周期间，将CsA包裹在脂质体中可使血清肌酐原本持续上升的情况出现统计学显著（p<0.05）下降。给予环孢素脂质体制剂后，近端肾小管上皮细胞形态正常，没有空泡化迹象，而空泡化是CsA肾毒性的特征，在环孢素溶液组中可见。虽然确切机制尚不清楚，但很可能当CsA包裹在脂质体中时，其组织分布发生了改变，有利于网状内皮细胞，从而使高敏感性但非靶器官如肾脏免受损害。
