Inclusion Complexes of Pachypodol with Unmodified and Modified Cyclodextrin Nanocarriers: Theoretical Studies

This study investigates the potential of alpha-, beta-, and gamma-cyclodextrins (α-CDX, β-CDX, and γ-CDX) and amino-, hydroxypropyl-, and random methyl-β-CDX (HPβ-CDX, AMβ-CDX, and RMβ-CDX) to enhance the water solubility, bioavailability, and stability of pachypodol (PAC) as with anticancer, antiviral, antimicrobial, anti-inflammatory, and antioxidant properties. Computational methods, e.g., molecular docking and molecular dynamics (MD) simulation methods, were utilized to analyze the CDXs: PAC ICs. The results show that the formation of a stable inclusion complex (IC) between HPβ-CDX and PAC is evident according to the molecular docking analysis. Furthermore, the insertion of PAC into the CDX cavities led to a decrease in the radial distribution function (RDF) graphs and a reduction in hydrogen bond numbers within the CDX cavities, compared with the free CDXs. HPβ-CDX exhibited the maximum number of hydrogen bonds with solvents because of its hydroxypropyl substituent. Furthermore, in keeping with molecular docking, the result of interaction energy revealed that Van der Waals (VDW) interaction and hydrogen bonding play a vital role in the CDXs: PAC IC formation. These results demonstrate the potential of both natural and modified CDXs as excipients to enhance the PAC’s stability, bioavailability, water solubility, and therapeutic activities.