Fiber Science and Apparel Design, Cornell University, Ithaca, New York 14853, United States.
Computational Science Research Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
Mol Pharm. 2021 Dec 6;18(12):4486-4500. doi: 10.1021/acs.molpharmaceut.1c00677. Epub 2021 Nov 15.
Prednisolone is a widely used immunosuppressive and anti-inflammatory drug type that suffers from low aqueous solubility and bioavailability. Due to the inclusion complexation with cyclodextrins (CDs), prednisolone's drawbacks that hinder its potential during the administration can be eliminated effectively. Here, we have early shown the electrospinning of free-standing nanofibrous webs of CD/prednisolone inclusion complexes (ICs) in the absence of a polymer matrix. In this study, hydroxypropyl-beta-CD (HPβCD) has been used to form ICs with prednisolone and generate nanofibrous webs with a drug loading capacity of ∼10% (w/w). Pullulan/prednisolone nanofibrous webs have been also fabricated as a control sample having the same drug loading (∼10%, w/w). It has been demonstrated that prednisolone has been found in an amorphous state in the HPβCD/prednisolone nanofibrous web due to inclusion complexation, while it has retained its crystal structure in the pullulan/prednisolone nanofibrous web. Therefore, the HPβCD/prednisolone IC nanofibrous web has shown a faster and enhanced release profile and superior disintegration feature in artificial saliva than the pullulan/prednisolone nanofibrous web. The complexation energy calculated using ab initio modeling displayed a more favorable interaction between HPβCD and prednisolone in the case of a molar ratio of 2:1 than 1:1 (CD: drug). Here, the HPβCD/prednisolone IC nanofibrous web has been developed without using a toxic component or solvent to dissolve drug molecules and boost drug loading in amorphous nature. The investigation of IC nanofibrous webs has been conducted to formulate a promising alternative to the orally disintegrating tablet formulation of prednisolone in the market. The nanofibrous structure and the improved physicochemical properties of prednisolone arising with the complexation might ensure a faster disintegration and onset of action against commercially available and orally disintegrating delivery systems during the desired treatment.
泼尼松龙是一种广泛应用的免疫抑制剂和抗炎药物,但其水溶性和生物利用度较低。通过与环糊精(CDs)形成包合物,可有效消除泼尼松龙在给药过程中阻碍其发挥潜力的缺陷。在这里,我们早期展示了在没有聚合物基质的情况下,自由-standing 纳米纤维网的静电纺丝 CD/泼尼松龙包合物(IC)。在这项研究中,羟丙基-β-CD(HPβCD)被用于与泼尼松龙形成 IC,并生成具有约 10%(w/w)载药量的纳米纤维网。作为对照样品,也制备了具有相同载药量(约 10%,w/w)的普鲁兰/泼尼松龙纳米纤维网。研究表明,由于包合作用,泼尼松龙在 HPβCD/泼尼松龙纳米纤维网中处于无定形态,而在普鲁兰/泼尼松龙纳米纤维网中保留了晶体结构。因此,HPβCD/泼尼松龙 IC 纳米纤维网在人工唾液中表现出更快、增强的释放特性和优于普鲁兰/泼尼松龙纳米纤维网的崩解特性。从头算建模计算的络合能显示,在摩尔比为 2:1 时,HPβCD 与泼尼松龙的相互作用比 1:1(CD:药物)更有利。在这里,HPβCD/泼尼松龙 IC 纳米纤维网是在不使用有毒成分或溶剂溶解药物分子并以无定形状态提高载药量的情况下开发的。对 IC 纳米纤维网的研究旨在为市场上的泼尼松龙口服崩解片制剂提供一种有前途的替代方案。与商业上可获得的口服崩解给药系统相比,复合物引起的纳米纤维结构和泼尼松龙物理化学性质的改善可能确保更快的崩解和起效。