Pharmacokinetic Study of Oral Disulfiram Suspension and Topical Transdermal Nano-Invasomes Gel in Wistar Rats

Abstract

Background: Disulfiram (DSF), an FDA-approved pharmaceutical for the management of alcoholism, has demonstrated its efficacy against several kinds of cancer. DSF has limited solubility, a fast metabolism, a short duration of action, and instability in physiological environments, mostly caused by rapid degradation in the acidic gastric environment. Objective: A transdermal gel containing disulfiram, which was loaded into invasomes, was developed to improve the stability of DSF and enable its effective distribution to tumor tissues. Methods: This study included 72 Wistar rats weighing 200±35 g, which were separated into two groups, each of which included 12 animals. Rats were orally provided a dose of 5 mg of pure DSF suspension via oral gavage, and DSF nano-invasomal transdermal gel was then applied to their skin. DSF is determined in rats' plasma by reverse-phase high-performance liquid chromatography (RP-HPLC). Results: The results showed that the maximum effect (Cmax, Tmax, and AUC0-72) were (Cmax=57.3±0.2, Tmax=3.6±0.01 and 562±3. 3ng.h/ml) for oral and (Cmax=138±0.4, Tmax=5.5±0.01 and 2819±6.6 ng. h/ml) for transdermal routes, respectively. Results showed that the time and concentration needed to achieve the maximum effect (Cmax and Tmax) were significantly different between DSF-oral suspension and transdermal invasomal gel (p<0.05). The relative bioavailability for the transdermal route was five times that of the oral route after a single dose administered for 72 hours. Conclusions: The nano-invasomal transdermal gel filled with DSF demonstrated a more convenient way of administering DSF compared to the oral route.