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

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ID: 282215
2025
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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. 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.
Reference Key
vats2025selfemulsifying Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Vats, Mukti; Rathod, Drishti; Patel, Henis; Richards, Terjahna; Patel, Ketan
Journal journal of molecular liquids
Year 2025
DOI
10.1016/j.molliq.2025.127161
URL
Keywords
oral bioavailability in silico modeling pancreatic adenocarcinoma soluplus pnd1186 self-emulsifying systems

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