Theoretical and Experimental Exploration of Multicomponent Forms of Cordycepin for Sustained Release

Cordycepin shows anticancer activity in vitro but minimal in vivo activity due to its short plasma half-life. To address this, the cocrystallization technique was used to prolong its release and protect it from deamination by adenosine deaminase. In this study, multiple simulation methods were combined to identify potential cocrystal formers (CCFs). Based on the simulation results, one binary salt (cordycepin-oxalic acid) and two binary cocrystals (cordycepin-gallic acid and cordycepin-vanillic acid) were successfully screened by the mechanochemical method. The new multicomponents were characterized by several techniques. In vitro dissolution experiments showed that the binary salt has a significant sustained-release effect. This study proposes a strategy using binary cocrystals/salts to achieve sustained release and increase the half-life of cordycepin, offering potential for its in vivo application.