Preparation and Characterization of SN-38-Encapsulated Phytantriol Cubosomes Containing α-Monoglyceride Additives
Preparation and Characterization of SN-38-Encapsulated Phytantriol Cubosomes Containing α-Monoglyceride Additives
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DOI：
10.1248/cpb.c15-00984
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发表时间：
2016-06-01
影响因子：
1.7
通讯作者：
Itai, Shigeru
中科院分区：
文献类型：
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作者：
Ali, Md Ashraf;Noguchi, Shuji;Itai, Shigeru
SN-38是伊立替康的一种强效活性代谢产物，被认为是一种抗癌候选药物。然而，该化合物的临床开发因其水溶性差和化学不稳定性而受到阻碍。在这项研究中，我们开发了SN-38包封的立方体来解决这些问题。使用六种α-单甘油酯添加剂，包括单辛酸甘油酯、单辛酸甘油酯、单月桂酸甘油酯、单肉豆蔻酸甘油酯、单棕榈酸甘油酯和单硬脂酸甘油酯，通过探针超声处理来制备植烷三醇（PHYT）立方体。这些体系的平均粒径、多分散指数和zeta电位值分别为约190- 230 nm、0.19-0.25和-17至-22 mV。小角X射线散射分析证实，无论有无添加剂，SN 38包裹的立方体都存在于酵母空间群上的Pn（3）中。与PHYT立方体相比，单甘油酯添加剂导致SN-38的溶解度增加约两倍。含添加剂的PHYT立方体药物包封率大于97%。在25 ° C下的稳定性研究的结果显示，粒度或多分散指数特征没有显著变化，10天后至少85%的SN-38以其活性内酯形式存在，证明了立方体纳米颗粒的高稳定性。此外，在体外生理条件下，约55%的SN-38在96 h内从添加剂的立方体中缓慢释放。总之，这些结果表明，SN-38包封的PHYT立方体颗粒是有前途的药物载体，应考虑用于进一步的体内实验，包括使用增强的渗透性和保留效应向肿瘤细胞递送药物。
SN-38 is a potent active metabolite of irinotecan that has been considered as an anticancer candidate. However, the clinical development of this compound has been hampered by its poor aqueous solubility and chemical instability. In this study, we developed SN-38-encapsulated cubosomes to resolve these problems. Six a-monoglyceride additives, comprising monocaprylin, monocaprin, monolaurin, monomyristin, monopalmitin, and monostearin, were used to prepare phytantriol (PHYT) cubosomes by probe sonication. The mean particle size, polydispersity index, and zeta potential values of these systems were around 190-230nm, 0.19-0.25 and -17 to -22 mV, respectively. Small-angle X-ray scattering analyses confirmed that the SN38-encapsulated cubosomes existed in the Pn (3) over barm space group both with and without the additives. The mono glyceride additives led to around a two-fold increase in the solubility of SN-38 compared with the PHYT cubosome. The drug entrapment efficiency of PHYT cubosomes with additives was greater than 97%. The results of a stability study at 25 degrees C showed no dramatic changes in the particle size or polydispersity index characteristics, with at least 85% of the SN-38 existing in its active lactone form after 10 d, demonstrating the high stability of the cubosome nanoparticles. Furthermore, approximately 55% of SN-38 was slowly released from the cubosomes with additives over 96h in vitro under physiological conditions. Taken together, these results show that the SN-38-encapsulated PHYT cubosome particles are promising drug carriers that should be considered for further in vivo experiments, including drug delivery to tumor cells using the enhanced permeability and retention effect.