Beta-cyclodextrin formulation of a disulfide-bond disrupting agent for improved systemic exposure.

ABSTRACT: Disulfide-bond disrupting agents (DDAs) are a class of cyclic thiosulfonates that have been shown to kill human epidermal growth factor receptor (HER) family-overexpressing breast cancer (BC) cells selectively and with no adverse side effects. Previous structure-activity relationships suggested a strong correlation between DDA lipophilicity and potency. In this study, we present the use of cyclodextrins (CDs) as molecular excipients to address the possible solubilizing drawback of increasingly lipophilic DDAs in oral administrations. The formulation of tcyDTDO, a potent second-generation DDA, with beta-cyclodextrin (BCD) and 2-hydroxypropyl-beta-cyclodextrin (HPB) was investigated. The choice of BCD as an optimal host over other CDs was guided by two in silico methods, namely: (1) h

SUBMITTER: Dulloo ZM 

PROVIDER: S-EPMC12124217 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature