Authors:

Andy Liu

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About Paper:

Each year, 1.3 million new cases of prostate cancer are reported across the globe. Bone metastases are the predominant prostate cancer complication in over 90% of severe patients, and castration-resistant cases elude a cure. Cabozantinib (cabo) and bemcentinib (BCT) are small molecule chemotherapeutics which target cellular receptors critical for prostate cancer tumor growth. However, both cabo and BCT are hydrophobic and have low oral bioavailability, limiting their effectiveness. The goal of this work was to encapsulate cabo or BCT into nanoparticles to develop intravenous and oral formulations with improved dissolution kinetics and efficacy. Flash NanoPrecipitation, an established antisolvent precipitation technique, was used to encapsulate Cabo or BCT into nanoparticles stabilized by an amphiphilic polymer shell. The size-stability of the resultant particles was monitored, and small and stable formulations were dialyzed against water to remove organic solvent and delay Ostwald ripening. After dialysis, all attempted cabo formulations were not stable below 400 nm in size. BCT formulations which incorporated vitamin E acetate remained stable at 50-70 nm for at least one-week post-dialysis, likely due to extremely hydrophobic vitamin E acetate providing favorable core nucleation sites. These BCT formulations were freeze-dried into powders and evaluated relative to unencapsulated BCT for in vitro dissolution kinetics and effective dosage. Based on these findings, the delivery and efficacy of BCT nanoparticles will be investigated in an animal model of bone metastatic prostate cancer.

Source:

Purdue University / 2023

Topics:

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Co-authors:

Andy Liu