Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 15:426:127161.
doi: 10.1016/j.molliq.2025.127161. Epub 2025 Feb 15.

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

Mukti Vats  1 , Drishti Rathod  1 , Henis Patel  1 , Terjahna Richards  1 , Ketan Patel  1
Affiliations

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

Mukti Vats et al. J Mol Liq. .

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.

Keywords: In silico modeling; Oral bioavailability; PND1186; Pancreatic Adenocarcinoma; Self-emulsifying Systems; Soluplus.

PubMed Disclaimer

References

    1. Sarantis P, Koustas E, Papadimitropoulou A, Papavassiliou AG, Karamouzis MV, Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy, World journal of gastrointestinal oncology 12(2) (2020) 173. DOI: 10.4251/wjgo.v12.i2.173 - DOI - PMC - PubMed
    1. Stoffel EM, Brand RE, Goggins M, Pancreatic cancer: changing epidemiology and new approaches to risk assessment, early detection, and prevention, Gastroenterology 164(5) (2023) 752–765. DOI: 10.1053/j.gastro.2023.02.012 - DOI - PMC - PubMed
    1. Bekkali NL, Oppong KW, Pancreatic ductal adenocarcinoma epidemiology and risk assessment: Could we prevent? Possibility for an early diagnosis, Endoscopic ultrasound 6(Suppl 3) (2017) S58. DOI: 10.4103/eus.eus_60_17 - DOI - PMC - PubMed
    1. Adamska A, Domenichini A, Falasca M, Pancreatic ductal adenocarcinoma: current and evolving therapies, International journal of molecular sciences 18(7) (2017) 1338. DOI: 10.3390/ijms18071338 - DOI - PMC - PubMed
    1. Tesfaye AA, Azmi AS, Philip PA, miRNA and gene expression in pancreatic ductal adenocarcinoma, The American journal of pathology 189(1) (2019) 58–70. DOI: 10.1016/j.ajpath.2018.10.005 - DOI - PMC - PubMed

LinkOut - more resources