Parthasarathy R, Sacks P G, Harris D, Brock H, Mehta K
Department of Clinical Investigation, University of Texas M.D. Anderson Cancer Center, Houston.
Cancer Chemother Pharmacol. 1994;34(6):527-34. doi: 10.1007/BF00685666.
Because of their antiproliferative and differentiation-inducing properties, retinoids have been used clinically as therapeutic and chemopreventive agents against squamous-cell carcinomas (SCC). As is the case for many therapeutic agents, however, the administration of retinoids is associated with toxic effects. Because encapsulation of certain drugs in lipid vesicles (liposomes) has been shown to result in reduced toxic effects, we studied the in vitro interaction of liposome-encapsulated all-trans-retinoic acid (L-ATRA) with a SCC line (MDA 886Ln) and its multicellular tumor spheroid (MTS) model. Various L-ATRA formulations were tested for incorporation of retinoic acid, toxic effects against human red blood cells, uptake and retention by tumor cells, and antiproliferative effects against SCC. Of the different formulations tested, L-ATRA containing diphosphatidyl palmitoylcholine (DPPC) and stearylamine (SA; 9:1, w/w) showed optimal drug incorporation, high stability, and minimal toxicity toward red blood cells and was highly efficacious in delivering ATRA and, thus, in inhibiting the growth of MDA 886Ln and its MTS model. DPPC: SA L-ATRA inhibited the expression of the enzyme keratinocyte transglutaminase in epidermal cells as effectively as did the free drug. These results suggest that liposomes can serve as an effective carrier system for the delivery of retinoids to SCC.
由于其抗增殖和诱导分化的特性，类视黄醇已在临床上用作治疗和化学预防鳞状细胞癌（SCC）的药物。然而，与许多治疗药物一样，类视黄醇的给药也会产生毒性作用。由于已证明将某些药物包裹在脂质囊泡（脂质体）中可降低毒性作用，我们研究了脂质体包裹的全反式维甲酸（L-ATRA）与SCC细胞系（MDA 886Ln）及其多细胞肿瘤球体（MTS）模型的体外相互作用。测试了各种L-ATRA制剂中维甲酸的掺入情况、对人红细胞的毒性作用、肿瘤细胞的摄取和保留情况以及对SCC的抗增殖作用。在所测试的不同制剂中，含有二棕榈酰磷脂酰胆碱（DPPC）和硬脂胺（SA；9:1，w/w）的L-ATRA显示出最佳的药物掺入、高稳定性以及对红细胞的最小毒性，并且在递送ATRA方面非常有效，从而能够抑制MDA 886Ln及其MTS模型的生长。DPPC:SA L-ATRA抑制表皮细胞中角质形成细胞转谷氨酰胺酶的表达效果与游离药物相同。这些结果表明脂质体可作为将类视黄醇递送至SCC的有效载体系统。
