Fiber Science Program, Department of Human Centered Design, College of Human Ecology, 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. 2023 May 1;20(5):2624-2633. doi: 10.1021/acs.molpharmaceut.3c00074. Epub 2023 Apr 4.
Griseofulvin (GSF) is one of the most widely used antifungal suffering from low water solubility and limited bioavailability. Here, cyclodextrin (CD) derivatives of hydroxypropyl-beta-CD (HPβCD) known for its high-water solubility were used to form inclusion complexes (ICs) with GSF. Here, the molecular modeling study revealed the more efficient complex formation with 1:2 (guest:CD) stoichiometry, so ICs of GSF-HPβCD were prepared using a 1:2 molar ratio (GSF:HPβCD) and then mixed with pullulan (PULL) to generate nanofibers (NFs) using the electrospinning technique. PULL is a nontoxic water-soluble biopolymer and the ultimate PULL/GSF-HPβCD-IC NF was obtained with a defect-free fiber morphology having 805 ± 180 nm average diameter. The self-standing and flexible PULL/GSF-HPβCD-IC NF was achieved to be produced with a loading efficiency of ∼98% corresponding to ∼6.4% (w/w) of drug content. In comparison, the control sample of PULL/GSF NF was formed with a lower loading efficiency value of ∼72% which equals to ∼4.7% (w/w) of GSF content. Additionally, PULL/GSF-HPβCD-IC NF provided an enhanced aqueous solubility for GSF compared to PULL/GSF NF so a faster release profile with ∼2.5 times higher released amount was obtained due to inclusion complexation between GSF and HPβCD within the nanofibrous web. On the other hand, both nanofibrous webs rapidly disintegrated (∼2 s) in the artificial saliva medium that mimics the oral cavity environment. Briefly, PULL/GSF-HPβCD-IC NF can be a promising dosage formulation as a fast-disintegrating delivery system for antifungal oral administration owing to the improved physicochemical properties of GSF.
灰黄霉素（GSF）是最广泛使用的抗真菌药物之一，但它的水溶性低，生物利用度有限。在这里，我们使用羟丙基-β-环糊精（HPβCD）的环糊精（CD）衍生物，因为它具有高水溶性，与 GSF 形成包合物（IC）。在这里，分子建模研究表明，1:2（客体：CD）化学计量比具有更有效的复合物形成，因此使用 1:2 摩尔比（GSF：HPβCD）制备 GSF-HPβCD 的 IC，然后与普鲁兰（PULL）混合使用静电纺丝技术生成纳米纤维（NFs）。PULL 是一种无毒的水溶性生物聚合物，最终得到的 PULL/GSF-HPβCD-IC NF 具有无缺陷的纤维形态，平均直径为 805±180nm。自支撑且灵活的 PULL/GSF-HPβCD-IC NF 的产量为 98%左右，载药量约为 6.4%（w/w）。相比之下，PULL/GSF NF 的对照样品的载药效率值较低，为 72%左右，相当于 GSF 含量为 4.7%（w/w）。此外，与 PULL/GSF NF 相比，PULL/GSF-HPβCD-IC NF 为 GSF 提供了增强的水溶解度，因此由于 GSF 与 HPβCD 之间的包合作用，在纳米纤维网络中获得了更快的释放曲线，释放量增加了约 2.5 倍。另一方面，两种纳米纤维网在模拟口腔环境的人工唾液介质中迅速崩解（约 2s）。简而言之，PULL/GSF-HPβCD-IC NF 可以作为一种快速崩解的抗真菌口腔给药递送系统，有望成为一种新的剂型，因为它改善了 GSF 的物理化学性质。
