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Updated: May 9, 2025
Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs
Published on: July 27, 2022
Self-emulsifying Nano-PND oral delivery systems of PND1186: In silico modeling for bioavailability estimation
Mukti Vats1, Drishti Rathod1, Henis Patel1
1College of Pharmacy and Health Sciences, St. John's University, NY, USA.
Abstract:
Focal adhesion kinase (FAK) inhibitors have proven to aid the therapeutic potential of anti-cancer agents. PND1186 (PND) is a FAK inhibitor disrupting the oncogenic processes such as cell survival, proliferation, adhesion, migration and angiogenesis, as well as remodeling of tumor microenvironment. However, the pharmacological potential of PND is limited by its poor solubility and bioavailability due to rapid precipitation of weakly basic PND in the intestinal milieu. As a solution, we have developed a self-nanoemulsifying PND oral delivery system (NanoPODS) for rapid dissolution of PND while Soluplus containing system (NanoPODS-S) was prepared to prevent the precipitation of PND. Optimized NanoPODS-S depicted a particle size of 107.0 ± 3.6 nm, PDI of 0.223 ± 0.016, and a surface potential of -4.2 ± 0.007 mV, along with > 70% PND released at pH 6.8. In silico pharmacokinetics predicted 99% oral bioavailability for NanoPODS-S. This study evaluates the efficacy of NanoPODS and NanoPODS-S for improved oral bioavailability with better cytotoxicity efficacy on Pancreatic Ductal Adenocarcinoma (PDAC) cell lines. NanoPODS-S is the first of its kind, self-nanoemulsifying system containing a polymeric precipitation inhibitor mimicking a "spring-parachute effect". It will be a novel platform technology for rapid and enhanced dissolution of poorly soluble molecules.
Insights
A novel self-nanoemulsifying drug delivery system, NanoPODS-S, enhances oral bioavailability and cytotoxicity of the FAK inhibitor PND1186 for pancreatic cancer treatment.
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.
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