Self-emulsifying Nano-PND oral delivery systems of PND1186: In silico modeling for bioavailability estimation

Area of Science:

• Pharmacology
• Nanotechnology
• Oncology

Background:

• Focal adhesion kinase (FAK) inhibitors show therapeutic promise in cancer treatment.
• PND1186 (PND), a FAK inhibitor, faces poor oral bioavailability due to rapid precipitation.
• This limits its potential for treating cancers like Pancreatic Ductal Adenocarcinoma (PDAC).

Purpose of the Study:

• To develop and evaluate a self-nanoemulsifying oral delivery system (NanoPODS) for PND.
• To improve PND's solubility, bioavailability, and anti-cancer efficacy, particularly for PDAC.
• To introduce NanoPODS-S, incorporating a polymeric precipitation inhibitor for enhanced drug release.

Main Methods:

• Development of self-nanoemulsifying systems (NanoPODS and NanoPODS-S) for PND.
• Characterization of NanoPODS-S: particle size, PDI, surface potential, and drug release at pH 6.8.
• In silico pharmacokinetic prediction of oral bioavailability.
• Evaluation of NanoPODS and NanoPODS-S efficacy on PDAC cell lines.

Main Results:

• Optimized NanoPODS-S showed a particle size of 107.0 ± 3.6 nm and PDI of 0.223 ± 0.016.
• NanoPODS-S achieved >70% PND release at pH 6.8 and predicted 99% oral bioavailability.
• The system demonstrated potential for improved cytotoxicity against PDAC cell lines.

Conclusions:

• NanoPODS-S represents a novel self-nanoemulsifying system with a unique "spring-parachute effect" for enhanced dissolution.
• This platform technology significantly improves oral bioavailability and anti-cancer efficacy of poorly soluble drugs like PND.
• NanoPODS-S holds promise for effective oral delivery of FAK inhibitors in cancer therapy.