Sakai Seiga, Hirano Yoshinori, Kobayashi Yusei, Arai Noriyoshi
Department of Mechanical Engineering, Keio University, Yokohama, Kanagawa 223-8522, Japan.
Soft Matter. 2023 Apr 26;19(16):2902-2907. doi: 10.1039/d2sm01542k.
Cyclodextrins (CDs) are suitable drug carriers because of their doughnut-shaped cavities with hydrophilic outer and hydrophobic inner surfaces. Temperature-responsive CD-based drug carriers are expected to be one of the most promising candidates for drug delivery systems. In this study, we performed molecular dynamics simulations of the inclusion complex of -CD with cyclophosphamide (CP) at temperatures from 300 K to 400 K to investigate the temperature dependency of the release behaviour of CP and structural changes of -CD in an aqueous solution. We analysed the distance between the centres of mass of -CD and CP and the radius of gyration of -CD. The CP molecule was released from the -CD cavity at 400 K, whereas two different inclusion complexes, partially and completely, were observed at < 400 K. -CD encapsulating a CP molecule had a more spherical shape and rigidity than -CD without a CP, and the rigidity of their inclusion complex decreased with increasing temperature. Our findings provide fundamental insights into the behaviours of the -CD/CP complex and drug release at the molecular level and can facilitate the development of new temperature-responsive drug delivery systems with CD nanocarriers triggered by localised temperature increases using focused ultrasound.
环糊精（CDs）是合适的药物载体，因为它们呈甜甜圈形状，具有亲水性外表面和疏水性内表面。基于温度响应的环糊精药物载体有望成为药物递送系统中最有前景的候选者之一。在本研究中，我们对β-环糊精（β-CD）与环磷酰胺（CP）的包合物在300 K至400 K温度范围内进行了分子动力学模拟，以研究水溶液中环磷酰胺释放行为的温度依赖性以及β-环糊精的结构变化。我们分析了β-环糊精和环磷酰胺质心之间的距离以及β-环糊精的回转半径。环磷酰胺分子在400 K时从β-环糊精空腔中释放出来，而在低于400 K时观察到两种不同的包合物，部分包合和完全包合。包封环磷酰胺分子的β-环糊精比未包封环磷酰胺的β-环糊精具有更球形的形状和更高的刚性，并且它们包合物的刚性随温度升高而降低。我们的研究结果为β-环糊精/环磷酰胺复合物的行为以及分子水平上的药物释放提供了基本见解，并有助于开发利用聚焦超声局部温度升高触发的新型环糊精纳米载体温度响应药物递送系统。
