High-capacity glycol chitosan-based nanoemulsion for efficient delivery of disulfiram

Abstract

Disulfiram (DS) is an anti-alcoholism drug capable of acting against important and hard-to-treat cancers. The drug’s relative instability and variable absorption/distribution have led to its variable pharmacokinetics and suboptimal exposure. Hence, it was hypothesised that a nano-enabled form of DS might be able to overcome such limitations. Encapsulation of the labile DS was achieved with quaternary ammonium palmitoyl glycol chitosan (GCPQ) to form a high-capacity, soybean oil-based DS-GCPQ nanoemulsion. DS-GCPQ showed capability of oil-loading up to 50% v/v for a stable entrapment of high drug content. With increasing oil content (10 to 50% v/v), the mean particle size and polydispersity index were also increased (166 to 351 nm and 0.14 to 0.22, respectively) for a given amount of GCPQ. Formulations showed a highly positive particle surface charge (50.9 ± 1.3 mV), contributing to the colloidal stability of the individual particles. DS-GCPQ showed marked cytotoxicity against pancreatic cancer cell lines with enhanced activity in the presence of copper. An intravenous pharmacokinetic study of DS-GCPQ in vivo showed improved plasma drug stability with a DS half-life of 17 min. Prolonged survival was seen in tumour-bearing animals treated with DS-GCPQ supplemented with copper. In conclusion, DS-GCPQ nanoemulsion has the potential to be developed further for cancer therapeutic purposes.