Egito E Sócrates T, Araújo Ivonete B, Damasceno Bolivar P G L, Price James C
Programa de Pós-graduação em Ciências Farmacêuticas (PPCF), Universidade Federal do Rio Grande do Norte (UFRN), Rua Praia de Areia Branca, 8948-Natal-RN, 59094-450, Brazil.
J Pharm Sci. 2002 Nov;91(11):2354-66. doi: 10.1002/jps.10223.
Mixing Fungizone with a fat emulsion used for nutritional purpose (Intralipid or Lipofundin ) was reported to decrease Amphotericin B (AmB) toxicity in clinical use. In an effort to understand the reason for this phenomenon, spectral and morphological analyses were done for the Fungizone and Fungizone /Lipofundin admixture (FLmix). The absorption spectra analyses showed that not only Fungizone but also FLmix presented spectra that were concentration dependent. Moreover, the spectra of FLmix remained stable until the concentration of 5 x 10(-7) M, and only at 5 x 10(-8) M did they become similar in shape to the Fungizone spectra. Morphological studies revealed that even though emulsion droplets with or without Fungizone presented the same particle size, the former was less electron dense compared with Lipofundin alone. These results suggest a kind of association between Fungizoneand Lipofundin that remains over the whole range of concentrations. This hypothesis was confirmed by in vitro studies in which FLmix presented an important selectivity against human and fungal cells compared with Fungizone. These findings suggest that parenteral emulsions should be able to reduce the AmB toxicity probably by changing the AmB self-association state by binding it with emulsion droplets.
据报道，在临床应用中，将两性霉素B（Fungizone）与用于营养目的的脂肪乳剂（英脱利匹特或力保肪宁）混合使用可降低两性霉素B（AmB）的毒性。为了弄清楚这一现象的原因，对两性霉素B和两性霉素B/力保肪宁混合物（FLmix）进行了光谱和形态分析。吸收光谱分析表明，不仅两性霉素B，而且FLmix的光谱都呈浓度依赖性。此外，FLmix的光谱在浓度达到5×10⁻⁷ M之前保持稳定，只有在浓度为5×10⁻⁸ M时，其形状才变得与两性霉素B的光谱相似。形态学研究表明，尽管含有或不含有两性霉素B的乳剂液滴粒径相同，但与单独的力保肪宁相比，前者的电子密度较低。这些结果表明，两性霉素B和力保肪宁之间存在一种在整个浓度范围内都存在的缔合。这一假设在体外研究中得到了证实，在该研究中，与两性霉素B相比，FLmix对人和真菌细胞具有重要的选择性。这些发现表明，胃肠外乳剂可能通过将AmB与乳剂液滴结合来改变AmB的自缔合状态，从而降低AmB的毒性。
