AI Article Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is tough to treat due to its low oxygen levels, and the study focuses on a drug called Vinblastine-N-Oxide (CPD100), which becomes active only in these hypoxic conditions.
- The researchers developed a form of CPD100 in liposomes (CPD100Li) that is small and stable, showing better penetration and effectiveness in cancer models compared to the regular CPD100.
- When combined with the standard treatment gemcitabine, CPD100Li demonstrated improved results, making it a promising candidate for future clinical use against PDAC.
Article Abstract
Pancreatic ductal adenocarcinoma (PDAC) presents as an unmet clinical challenge for drug delivery due to its unique hypoxic biology. Vinblastine-N-Oxide (CPD100) is a hypoxia-activated prodrug (HAP) that selectively converts to its parent compound, vinblastine, a potent cytotoxic agent, under oxygen gradient. The study evaluates the efficacy of microfluidics formulated liposomal CPD100 (CPD100Li) in PDAC. CPD100Li were formulated with a size of 95 nm and a polydispersity index of 0.2. CPD100Li was stable for a period of 18 months when freeze-dried at a concentration of 3.55 mg/mL. CPD100 and CPD100Li confirmed selective activation at low oxygen levels in pancreatic cancer cell lines. Moreover, in 3D spheroids, CPD100Li displayed higher penetration and disruption compared to CPD100. In patient-derived 3D organoids, CPD100Li exhibited higher cell inhibition in the organoids that displayed higher expression of hypoxia-inducible factor 1 alpha (HIF1A) compared to CPD100. In the orthotopic model, the combination of CPD100Li with gemcitabine (GEM) (standard of care for PDAC) showed higher efficacy than CPD100Li alone for a period of 90 days. In summary, the evaluation of CPD100Li in multiple cellular models provides a strong foundation for its clinical application in PDAC.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031349 | PMC |
| http://dx.doi.org/10.3390/pharmaceutics14040713 | DOI Listing |
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