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

作者信息

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

机构信息

College of Pharmacy and Health Sciences, St. John's University, NY, USA.

出版信息

J Mol Liq. 2025 May 15;426. doi: 10.1016/j.molliq.2025.127161. Epub 2025 Feb 15.


DOI:10.1016/j.molliq.2025.127161
PMID:40322757
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12048016/
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.

摘要

相似文献

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

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本文引用的文献

[1]
Chitosan/bovine serum albumin layer-by-layer assembled particles for non-invasive inhaled drug delivery to the lungs.

Int J Biol Macromol. 2024-6

[2]
Roles and inhibitors of FAK in cancer: current advances and future directions.

Front Pharmacol. 2024-2-12

[3]
Focal adhesion kinase: from biological functions to therapeutic strategies.

Exp Hematol Oncol. 2023-9-25

[4]
Study on the relationships between the oil HLB value and emulsion stabilization.

RSC Adv. 2023-8-18

[5]
Interlaboratory Variability in the Madin-Darby Canine Kidney Cell Proteome.

Mol Pharm. 2023-7-3

[6]
Ibrutinib amorphous solid dispersions with enhanced dissolution at colonic pH for the localized treatment of colorectal cancer.

Int J Pharm. 2023-6-25

[7]
Pancreatic Cancer: Changing Epidemiology and New Approaches to Risk Assessment, Early Detection, and Prevention.

Gastroenterology. 2023-4

[8]
Palmitoyl Carnitine-Anchored Nanoliposomes for Neovasculature-Specific Delivery of Gemcitabine Elaidate to Treat Pancreatic Cancer.

Cancers (Basel). 2022-12-28

[9]
Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers-A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs.

Pharmaceuticals (Basel). 2022-9-11

[10]
Immunomodulatory effects of regorafenib: Enhancing the efficacy of anti-PD-1/PD-L1 therapy.

Front Immunol. 2022

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