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.
The application of layer-by-layer (LbL) approach on nanoparticle surface coating improves the colon-specific drug delivery of insoluble drugs. Here, we aimed to formulate a self-assembled cysteamine-based disulphide cross-linked sodium alginate with LbL self-assembly to improve the delivery of paclitaxel (PCX) to colonic cancer cells. Cysteamine was conjugated to the backbone of oxidized SA to form a core of self-assembled disulphide cross-linked nanospheres. P3DL was selected for PCX loading and fabricated LbL with poly(allylamine hydrochloride) (PAH) and poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSCMA) resulting from characterization and drug release studies. P3DL-fabricated PCX-loaded nanospheres (P3DL/PAH/PSSCMA) exhibited an encapsulation efficiency of 77.1% with cumulative drug release of 45.1%. Dynamic light scattering analysis was reported at 173.6 ± 2.5 nm with polydispersity index of 0.394 ± 0.105 (zeta potential= -58.5 mV). P3DL/PAH/PSSCMA demonstrated a pH-dependent swelling transition; from pH 1 to 7 (102.2% increase). The size increased by 33.0% in reduction response study after incubating with 10 mM glutathione (day 7). HT-29 cells showed high viabilities (86.7%) after treatment with the fabricated nanospheres at 0.8 µg/mL. Cellular internalization was successful with more than 70.0% nanospheres detected in HT-29 cells. Therefore, this fabricated nanospheres may be considered as potential nanocarriers for colon cancer-targeted chemotherapeutic drug delivery.