Faculty of Chemistry and Pharmacy, Sofia University "St. Kliment Ohridski", 1164, Sofia, Bulgaria.
Institute of Optical Materials and Technologies "Acad. J. Malinowski", Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria.
J Mol Graph Model. 2023 Mar;119:108380. doi: 10.1016/j.jmgm.2022.108380. Epub 2022 Nov 22.
Cucurbiturils are useful excipients in eye drop formulations: they can increase the water solubility of the drug, enhance drug absorption into the eye, improve aqueous stability and reduce local irritation. Effective and safe drug delivery is, however, a challenge and the information on the host (CBs)/guest (tropicamide and atropine) interactions can help improving the existing treatments and develop novel therapies not limited only to eye diseases/conditions. Since this carrier system can easily modify the properties of the drug and ensure its delivery at the targeted ocular tissue, further insight into the intimate mechanism of the host-guest recognition is crucial. The present DFT/SMD study focuses on the role of numerous factors governing this process, namely the specific position of the guest molecule in the cavity of the cucurbituril, the ionization form (non/protonated) of the antimuscarinic drug, the dielectric constant of the medium, and the size of the cavitant pore. The obtained results are in line with experimental observations and shed light on the mechanism, at atomic resolution, of recognition between the CBs and the two parasympatholytic drugs.
它们可以提高药物的水溶性，增强药物在眼部的吸收，提高水稳定性并减少局部刺激。然而，有效的和安全的药物输送是一个挑战，关于主体（葫芦脲）/客体（托吡卡胺和阿托品）相互作用的信息可以帮助改进现有的治疗方法并开发新的治疗方法，而不仅仅局限于眼部疾病/病症。由于该载体系统可以轻松改变药物的性质并确保其递送到靶向眼部组织，因此深入了解主体-客体识别的内在机制至关重要。本 DFT/SMD 研究重点关注控制该过程的众多因素的作用，即客体分子在葫芦脲腔中的特定位置、抗毒蕈碱药物的电离形式（非质子化/质子化）、介质的介电常数和空腔的大小。所得结果与实验观察结果一致，并阐明了葫芦脲与两种拟副交感神经药物之间识别的原子分辨率机制。
