Department of Pharmacy, Songjiang Hospital Affiliated The First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China ; Shanghai Songjiang Hospital Affiliated Nanjing Medical University, Nanjing, People's Republic of China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People's Republic of China.
Int J Nanomedicine. 2014;9:327-36. doi: 10.2147/IJN.S54967. Epub 2014 Jan 6.
The oral administration of amphotericin B (AmB) has a major drawback of poor bioavailability. The aim of this study was to investigate the potential of glyceryl monoolein (GMO) cubosomes as lipid nanocarriers to improve the oral efficacy of AmB. Antifungal efficacy was determined in vivo in rats after oral administration, to investigate its therapeutic use. The human colon adenocarcinoma cell line (Caco-2) was used in vitro to evaluate transport across a model of the intestinal barrier. In vivo antifungal results showed that AmB, loaded in GMO cubosomes, could significantly enhance oral efficacy, compared against Fungizone, and that during a 2 day course of dosage 10 mg/kg the drug reached effective therapeutic concentrations in renal tissue for treating fungal infections. In the Caco-2 transport studies, GMO cubosomes resulted in a significantly larger amount of AmB being transported into Caco-2 cells, via both clathrin- and caveolae-mediated endocytosis, but not macropinocytosis. These results suggest that GMO cubosomes, as lipid nanovectors, could facilitate the oral delivery of AmB.
口服两性霉素 B（AmB）存在生物利用度差的主要缺点。本研究旨在研究甘油脂单油酸酯（GMO）立方相作为脂质纳米载体的潜力，以提高 AmB 的口服疗效。在大鼠体内进行了口服给药后的抗真菌功效研究，以探讨其治疗用途。在体外用人结肠腺癌细胞系（Caco-2）评估穿过肠道屏障模型的转运。体内抗真菌结果表明，与 Fungizone 相比，负载在 GMO 立方相中的 AmB 能够显著提高口服疗效，并且在剂量为 10mg/kg 的 2 天疗程中，药物在肾脏组织中达到了有效治疗真菌感染的浓度。在 Caco-2 转运研究中，GMO 立方相通过网格蛋白和小窝介导的内吞作用，但不是巨胞饮作用，导致更多的 AmB 被转运到 Caco-2 细胞中。这些结果表明，GMO 立方相作为脂质纳米载体，可以促进 AmB 的口服递送。
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