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用于快速溶解口服给药系统的氢化可的松/环糊精复合物电纺纳米纤维

Hydrocortisone/cyclodextrin complex electrospun nanofibers for a fast-dissolving oral drug delivery system.

作者信息

Celebioglu Asli, Uyar Tamer

机构信息

Department of Fiber Science & Apparel Design , College of Human Ecology , Cornell University , Ithaca , NY 14853 , USA . Email:

出版信息

RSC Med Chem. 2020 Jan 8;11(2):245-258. doi: 10.1039/c9md00390h. eCollection 2020 Feb 1.

Abstract

The electrospinning of hydrocortisone/cyclodextrin complex nanofibers was performed in order to develop a fast-dissolving oral drug delivery system. Hydrocortisone is a water-insoluble hydrophobic drug, yet, the water solubility of hydrocortisone was significantly enhanced by inclusion complexation with hydroxypropyl-beta-cyclodextrin (HP-β-CyD). In this study, hydrocortisone/HP-β-CyD complexes were prepared in aqueous solutions having molar ratios of 1/1, 1/1.5 and 1/2 (hydrocortisone/HP-β-CyD). Highly concentrated aqueous solutions of HP-β-CyD (180%, w/v) were used for hydrocortisone/HP-β-CyD systems (1/1, 1/1.5 and 1/2) in order to perform electrospinning without the use of an additional polymer matrix. The turbidity of hydrocortisone/HP-β-CyD (1/1 and 1/1.5) aqueous solutions indicated the presence of some uncomplexed crystals of hydrocortisone whereas the aqueous solution of hydrocortisone/HP-β-CyD (1/2) was homogeneous indicating that hydrocortisone becomes totally water-soluble by inclusion complexation with HP-β-CyD. Nonetheless, the electrospinning of hydrocortisone/HP-β-CyD systems (1/1, 1/1.5 and 1/2) successfully yielded defect-free uniform nanofibrous structures. Moreover, the electrospinning process was quite efficient that hydrocortisone was completely preserved without any loss yielding hydrocortisone/HP-β-CyD nanofibers having the initial molar ratios (1/1, 1/1.5 and 1/2). The structural and thermal characterization of the hydrocortisone/HP-β-CyD nanofibers revealed that hydrocortisone was totally inclusion complexed with HP-β-CyD and was in the amorphous state in hydrocortisone/HP-β-CyD (1/2) nanofibers whereas some uncomplexed crystalline hydrocortisone was present in hydrocortisone/HP-β-CyD (1/1 and 1/1.5) nanofibers. Nevertheless, hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) complex aqueous systems were electrospun in the form of nanofibrous webs having a free-standing and flexible nature. The hydrocortisone/HP-β-CyD (1/1, 1/1.5 and 1/2) nanofibrous webs have shown fast-dissolving behavior in water or when they were in contact with artificial saliva. Yet, the hydrocortisone/HP-β-CyD (1/2) nanofibrous web dissolved more quickly than the hydrocortisone/HP-β-CyD (1/1 and 1/1.5) nanofibrous webs due to the full inclusion complexation and the amorphous state of hydrocortisone in this sample. In short, the results suggest that polymer-free electrospun nanofibrous webs produced from hydrocortisone/HP-β-CyD could be quite applicable for fast-dissolving oral drug delivery systems.

摘要

为开发一种速溶口服给药系统,进行了氢化可的松/环糊精复合纳米纤维的静电纺丝。氢化可的松是一种水不溶性疏水性药物,然而,通过与羟丙基-β-环糊精(HP-β-CyD)形成包合物,氢化可的松的水溶性显著提高。在本研究中,氢化可的松/HP-β-CyD复合物在摩尔比为1/1、1/1.5和1/2(氢化可的松/HP-β-CyD)的水溶液中制备。为了在不使用额外聚合物基质的情况下进行静电纺丝,HP-β-CyD的高浓度水溶液(180%,w/v)用于氢化可的松/HP-β-CyD体系(1/1、1/1.5和1/2)。氢化可的松/HP-β-CyD(1/1和1/1.5)水溶液的浊度表明存在一些未复合的氢化可的松晶体,而氢化可的松/HP-β-CyD(1/2)水溶液是均匀的,这表明氢化可的松通过与HP-β-CyD形成包合物而完全水溶。尽管如此,氢化可的松/HP-β-CyD体系(1/1、1/1.5和1/2)的静电纺丝成功地产生了无缺陷的均匀纳米纤维结构。此外,静电纺丝过程非常高效,氢化可的松完全保留,没有任何损失,得到了具有初始摩尔比(1/1、1/1.5和1/2)的氢化可的松/HP-β-CyD纳米纤维。氢化可的松/HP-β-CyD纳米纤维的结构和热表征表明,氢化可的松在氢化可的松/HP-β-CyD(1/2)纳米纤维中与HP-β-CyD完全形成包合物且处于无定形状态,而在氢化可的松/HP-β-CyD(1/1和1/1.5)纳米纤维中存在一些未复合的结晶氢化可的松。然而,氢化可的松/HP-β-CyD(1/1、1/1.5和1/2)复合水体系以具有自立性和柔韧性的纳米纤维网形式进行静电纺丝。氢化可的松/HP-β-CyD(1/1、1/1.5和1/2)纳米纤维网在水中或与人工唾液接触时表现出速溶行为。然而,由于该样品中氢化可的松的完全包合络合和无定形状态,氢化可的松/HP-β-CyD(1/2)纳米纤维网比氢化可的松/HP-β-CyD(1/1和1/1.5)纳米纤维网溶解得更快。简而言之,结果表明,由氢化可的松/HP-β-CyD制备的无聚合物静电纺纳米纤维网可非常适用于速溶口服给药系统。

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