Tonetti M, Astroff B, Satterfield W, De Flora A, Benatti U, DeLoach J R
Veterinary Toxicology, USDA-ARS, College Station, Texas 77840.
Biotechnol Appl Biochem. 1990 Dec;12(6):621-9.
Adriamycin was internalized in canine red blood cells (RBC) by two procedures involving (a) simple diffusion of the drug into cells and (b) hypotonic dialysis followed by isotonic resealing. The two procedures yielded comparable amounts of encapsulated adriamycin, around 35 micrograms/10(9) RBC. Exposure of adriamycin-loaded RBC to 0.16% glutaraldehyde consistently slowed down the rate of efflux of the drug as compared with non-glutaraldehyde-treated cells: after 1 h of incubation at 37 degrees C, greater than 80% of adriamycin was still present inside the glutaraldehyde-treated RBC, while at 24 h it was 66%, compared to 10% and 1%, respectively, in the adriamycin-loaded, non-glutaraldehyde-treated cells. Canine RBC showed a higher rate of transformation of adriamycin than the human cells, the only intracellular metabolite being adriamycinol, which is apparently formed by the NADPH-dependent enzyme aldehyde reductase. Production of adriamycinol was remarkably lower in the glutaraldehyde-treated RBC, as a result of progressive and extensive inactivation of hexose monophosphate shunt activity responsible for NADPH formation. These results, coupled with the known selective targeting of glutaraldehyde-treated RBC to liver, hold promise as to in vivo applications of this drug delivery system in antineoplastic therapy.
阿霉素通过两种方法被犬红细胞（RBC）摄取，这两种方法包括：（a）药物简单扩散进入细胞；（b）低渗透析后等渗重封。这两种方法产生的包封阿霉素量相当，约为35微克/10⁹个红细胞。与未用戊二醛处理的细胞相比，将负载阿霉素的红细胞暴露于0.16%戊二醛会持续减缓药物的外排速率：在37℃孵育1小时后，超过80%的阿霉素仍存在于经戊二醛处理的红细胞内，而在24小时时为66%，相比之下，负载阿霉素的未用戊二醛处理的细胞分别为10%和1%。犬红细胞显示出比人类细胞更高的阿霉素转化速率，唯一的细胞内代谢产物是阿霉素醇，它显然是由依赖NADPH的醛还原酶形成的。由于负责NADPH形成的磷酸己糖旁路活性逐渐广泛失活，经戊二醛处理的红细胞中阿霉素醇的产生显著降低。这些结果，再加上已知经戊二醛处理的红细胞对肝脏具有选择性靶向作用，为这种药物递送系统在抗肿瘤治疗中的体内应用带来了希望。
