Circumstantial Overdose Management of an Efficient Cancer Cell Photosensitizer with Preclinical Evidence: A Biophysical Study.

Abstract

In this article, pharmacological management of circumstantial overdose of an anticancer drug, Harmine (HM), under in vitro and in vivo conditions is described and further validated by employing in silico methods. HM, an efficient cancer cell photosensitizer, interacts extensively with nontoxic β-cyclodextrin (β-CD). Steady-state fluorescence studies and molecular docking analysis established differential nature of molecular inclusion depending on the relative concentrations of β-CD. Presently, β-CD is commonly used as a standard drug-delivery vehicle but its application for controlled drug withdrawal is rarely explored. Flow cytometric results and in vivo investigations on a zebrafish model showed that conditional overdose of preadministered drug molecules can be efficiently removed by encapsulating successfully within nontoxic β-CDs, albeit by controlled application of the same. This is an approach to manage the cytotoxicity of a drug in a safe way that is already administered. We believe that this β-CD-mediated withdrawal of drugs may find possible applications in controlled capturing of excess or unused drug inside living systems and reducing the unwanted toxicity associated with chemotherapeutics.