NERDG 2026
Poster 7 Abstract
Hydrophobic ion pairing facilitated self-Nanoemulsifying Drug Delivery System of Niclosamide for cancer treatment
Bhoomi Dholariya, Ketan Patel
College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11432
Presenting Author: Bhoomi Dholariya
Corresponding Author: Ketan Patel, [email protected]
Purpose
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited first-line treatment options. Niclosamide (NIC) has been widely explored as an anticancer agent, but its efficacy is significantly limited by insufficient systemic concentration upon oral administration. It is a brick dust molecule with poor aqueous and lipid solubility. To address these challenges, we adopted a hybrid approach – hydrophobic ion pairing in self-nanoemulsifying drug delivery system to enhance the drug loading, aqueous solubility and permeability.
Methods
An array of biocompatible solvents was screened for preparing self-nanoemulsifying drug delivery system (SNEDDS). A defined ratio of medium-chain triglycerides and surfactant (MCT:ELP) was employed as the oil–surfactant system. Due to limited solubility of NIC in oil &lipids, hydrophobic ion pairing agents were screened to improve drug loading. Cationic and ionizable lipid including oleyl amine, DOTAP and D-Lin-DMA were tested for biocompatibility and complexation efficiency with anionic NIC. The particle size and zeta potential of the formulation and blank formulation were measured.
Results
Though, lower complexation efficiency with NIC, an ionizable lipid was found to be significantly biocompatible over oleyl amine and DOTAP. The particle size of the optimized formulation was 23.67±1.2 nm with a zeta potential of +15.5±0.56 mV while particle size and zeta potential of the DLin-DMA-based blank formulation were 18.35±0.99 nm and +18±0.69 mV, respectively. Hydrophobic ion pairing not only improved the drug loading by 3 fold but prevented the precipitation of NIC on dispersion in phosphate buffer pH 7.4. The IC₅₀ of NIC nanoformulation was significantly lower in MiaPaCa-2 and PANC-1 cells. Optimized formulation remained neutral at physiological pH and cationic at lower pH, making it a suitable candidate for formulation development. Predictive pharmacokinetic modelling using Gastroplus is ongoing.
Conclusion
A hydrophobic ion pairing approach with ionizable lipid enabled the development of a self-nanoemulsifying drug delivery system of NIC. Drug loading, stability and aqueous solubility of an anionic hydrophobic molecule could be significantly improved by a biocompatible ionizable lipid.
Keywords
Pancreatic cancer, Niclosamide, Hydrophobic Ion-pairing complexation, Self-nanoemulsifying drug delivery systems
Poster 7 Abstract
Hydrophobic ion pairing facilitated self-Nanoemulsifying Drug Delivery System of Niclosamide for cancer treatment
Bhoomi Dholariya, Ketan Patel
College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11432
Presenting Author: Bhoomi Dholariya
Corresponding Author: Ketan Patel, [email protected]
Purpose
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited first-line treatment options. Niclosamide (NIC) has been widely explored as an anticancer agent, but its efficacy is significantly limited by insufficient systemic concentration upon oral administration. It is a brick dust molecule with poor aqueous and lipid solubility. To address these challenges, we adopted a hybrid approach – hydrophobic ion pairing in self-nanoemulsifying drug delivery system to enhance the drug loading, aqueous solubility and permeability.
Methods
An array of biocompatible solvents was screened for preparing self-nanoemulsifying drug delivery system (SNEDDS). A defined ratio of medium-chain triglycerides and surfactant (MCT:ELP) was employed as the oil–surfactant system. Due to limited solubility of NIC in oil &lipids, hydrophobic ion pairing agents were screened to improve drug loading. Cationic and ionizable lipid including oleyl amine, DOTAP and D-Lin-DMA were tested for biocompatibility and complexation efficiency with anionic NIC. The particle size and zeta potential of the formulation and blank formulation were measured.
Results
Though, lower complexation efficiency with NIC, an ionizable lipid was found to be significantly biocompatible over oleyl amine and DOTAP. The particle size of the optimized formulation was 23.67±1.2 nm with a zeta potential of +15.5±0.56 mV while particle size and zeta potential of the DLin-DMA-based blank formulation were 18.35±0.99 nm and +18±0.69 mV, respectively. Hydrophobic ion pairing not only improved the drug loading by 3 fold but prevented the precipitation of NIC on dispersion in phosphate buffer pH 7.4. The IC₅₀ of NIC nanoformulation was significantly lower in MiaPaCa-2 and PANC-1 cells. Optimized formulation remained neutral at physiological pH and cationic at lower pH, making it a suitable candidate for formulation development. Predictive pharmacokinetic modelling using Gastroplus is ongoing.
Conclusion
A hydrophobic ion pairing approach with ionizable lipid enabled the development of a self-nanoemulsifying drug delivery system of NIC. Drug loading, stability and aqueous solubility of an anionic hydrophobic molecule could be significantly improved by a biocompatible ionizable lipid.
Keywords
Pancreatic cancer, Niclosamide, Hydrophobic Ion-pairing complexation, Self-nanoemulsifying drug delivery systems
