PEG-PLGA from PolySciTech used in the development of nanoparticles to deliver anti-tumor agents RG7388 and entinostat for cancer therapy

 

In cancer therapy applications it is possible for specific drugs to work in concert creating a stronger effect than either of them would have on their own. Due to their interactions on several biological pathways, there is good indication that recently discovered RG7388 compound can work with entinostat to treat cancer. Researchers at Queen’s University Belfast and Al-Ahliyya Amman University used PEG-PLGA (Cat# AK010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create and test the efficacy of nanoparticles loaded with both drugs. This research holds promise to improve cancer therapy in the future. Read more: Abed, Anas, Michelle K. Greene, Alhareth A. Alsa’d, Andrea Lees, Andrew Hindley, Daniel B. Longley, Simon S. McDade, and Christopher J. Scott. "Nanoencapsulation of MDM2 Inhibitor RG7388 and Class-I HDAC Inhibitor Entinostat Enhances their Therapeutic Potential Through Synergistic Antitumor Effects and Reduction of Systemic Toxicity." Molecular Pharmaceutics (2024). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.3c00926

“Inhibitors of the p53–MDM2 interaction such as RG7388 have been developed to exploit latent tumor suppressive properties in p53 in 50% of tumors in which p53 is wild-type. However, these agents for the most part activate cell cycle arrest rather than death, and high doses in patients elicit on-target dose-limiting neutropenia. Recent work from our group indicates that combination of p53–MDM2 inhibitors with the class-I HDAC inhibitor Entinostat (which itself has dose-limiting toxicity issues) has the potential to significantly augment cell death in p53 wild-type colorectal cancer cells. We investigated whether coencapsulation of RG7388 and Entinostat within polymeric nanoparticles (NPs) could overcome efficacy and toxicity limitations of this drug combination. Combinations of RG7388 and Entinostat across a range of different molar ratios resulted in synergistic increases in cell death when delivered in both free drug and nanoencapsulated formats in all colorectal cell lines tested. Importantly, we also explored the in vivo impact of the drug combination on murine blood leukocytes, showing that the leukopenia induced by the free drugs could be significantly mitigated by nanoencapsulation. Taken together, this study demonstrates that formulating these agents within a single nanoparticle delivery platform may provide clinical utility beyond use as nonencapsulated agents. KEYWORDS:cancer nanoparticles Entinostat nutlin toxicity combination therapy”

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