# Development, Optimization, and Evaluation of Nano Self-Emulsifying Drug Delivery System Formulation Platform for Oral Bioavailability Enhancement of Sulfasalazine and Disulfiram in Lung Cancer Chemoprevention

## TL;DR

This study develops a new drug delivery system to improve the absorption of two drugs for lung cancer prevention.

## Contribution

A novel nano self-emulsifying drug delivery system was developed to enhance the bioavailability of sulfasalazine and disulfiram.

## Key findings

- Nano-SEDDS formulations showed 4.5-fold and 3.75-fold improvement in drug dissolution.
- Sulfasalazine Nano-SEDDS increased oral bioavailability by 7.9-fold.
- Formulations were stable at room temperature following ICH guidelines.

## Abstract

Lung cancer chemoprevention modalities are gaining wide attention as it is the second most diagnosed cancer type and the leading cause of cancer-related deaths. Our previous studies reported unique lung cancer chemoprevention capability with a repurposed drug combination of sulfasalazine (SAS) and disulfiram (DSF). However, their efficacy is limited by poor bioavailability. To overcome this challenge, we developed bioenhanced oil-in-water (o/w) nano self-emulsifying drug delivery system (Nano-SEDDS) formulations of SAS and DSF.

Unique isotropic Nano-SEDDS of SAS and DSF were developed and optimized using a single-step mix method followed by in vitro physicochemical characterization and stability studies. An in vivo pharmacokinetic and tissue-biodistribution study was undertaken to test the proposed hypothesis of bioavailability enhancement with Nano-SEDDS of SAS and DSF.

The optimal Nano-SEDDS formulation exhibited low nanodroplet sizes (< 200 nm), high drug content, and 4.5-fold (p < 0.01) and 3.75-fold (p < 0.01) enhancement in in vitro dissolution of SAS and DSF compared to the respective free drugs. The Nano-SEDDS formulations were also confirmed to be stable at room temperature in compliance with ICH guidelines. Further, SAS Nano-SEDDS showed a dose-dependent increment in oral bioavailability as shown by a significant 7.9-fold (p < 0.0001) enhancement in dose-normalized AUC at a dose of 10 mg/kg compared to free drug treatment at a control dose of 250 mg/kg.

Overall, the studies corroborated the successful formulation of bioavailability-enhanced SAS and DSF Nano-SEDDS with future co-delivery applications for lung cancer prevention.