Enhancing Water Solubility and Stability of Natamycin by Molecular Encapsulation in Methyl-β-Cyclodextrin and its Mechanisms by Molecular Dynamics Simulations

In this study, the antifungal compound natamycin was encapsulated in methyl- β -cyclodextrin (heptakis(2,6-di-O-methyl)- β -cyclodextrin, Me- β -CD) to improve its aqueous solubility and stability. The aqueous solubilities of natamycin in the presence of β -CD, 2-hydroxypropyl- β -CD, 6-O- α -maltosyl- β -CD, and Me- β -CD were compared. The Me- β -CD showed the best result to increase the solubility of natamycin in aqueous. The pH stability of natamycin was improved by the formation of inclusion complex with Me- β -CD, especially at acidic conditions. The degradation of natamycin under UV-light exposure followed first-order kinetics with half-life times ( t 1/2 ) of 59.2 and 157.5 min in pure form and Me- β -CD inclusion complex, respectively. The in vitro antifungal activities of natamycin/Me -β -CD complex against Aspergillus niger food pathogen were evaluated. The results demonstrated that the natamycin/Me -β -CD complex could effectively improve the aqueous solubility and photostability of natamycin without compromising in antifungal activities. Finally, the molecular inclusion mechanisms and geometrical configurations of the natamycin/Me -β -CD complex were studied using molecular dynamics simulations. This research may lead to the development of more effective inclusion-based delivery systems to encapsulate and protect lipophilic antimicrobial agents for food applications.