curcumin and benzeneboronic-acid

Topics: Antineoplastic Agents; Boronic Acids; Curcumin; Drug Carriers; Drug Delivery Systems; Hydrogen Peroxide; Micelles; Nanoparticles; Polyethylene Glycols

Along with the successful commercialization of chemotherapeutics, such as doxorubicin and paclitaxel, numerous natural compounds have been investigated for clinical applications. Recently, curcumin (CUR), a natural compound with various therapeutic effects, has attracted attention for cancer immunotherapy. Most chemotherapeutics, however, have poor water solubility due to their hydrophobicity, which makes them less suited to biomedical applications; CUR is no exception because of its low bioavailability and extremely high hydrophobicity. In the present study, we developed an easy but effective strategy using the interaction between the 1,3-dicarbonyl groups of drugs and phenylboronic acid (PBA) to solubilize hydrophobic drugs. First, we verified the coordinate interaction between 1,3-dicarbonyl and PBA using 3,5-heptanedione as a model compound, followed by CUR as a model drug. A PBA-grafted hydrophilic polymer was used to form a nanoconstruct by coordination bonding with CUR, which then made direct administration of the nanoparticles possible. The nanoconstruct exhibited remarkable loading capability, uniform size, colloidal stability, and pH-responsive drug release, attributed to the formation of core-shell nanoconstructs by coordinate interaction. The therapeutic nanoconstructs successfully showed both chemotherapeutic and anti-PD-L1 anticancer effects in cellular and animal models. Furthermore, we demonstrated the applicability of this technique to other 1,3-dicarbonyl compounds. Overall, our findings suggest a facile, but expandable strategy by applying the coordinate interaction between 1,3-dicarbonyl and PBA, which enables high drug loading and stimuli-responsive drug release.

Topics: Animals; Antineoplastic Agents; Boronic Acids; Curcumin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Nanoparticles; Pharmaceutical Preparations

In order to achieve high loading and efficient delivery of curcumin, phenylboronic acid-conjugated chitosan nanoparticles were prepared by a simple desolvation method. These nanoparticles exhibited a regular spherical shape with the average size about 200-230 nm and narrow size distribution, which were kinetically stable under physiological condition. Due to boronate ester formation between curcumin and phenylboronic acid groups in the nanoparticles, and the hydrogen bonding interactions between curcumin and nanocarriers, curcumin was successfully loaded into the nanoparticles with high drug loading content. These curcumin-loaded nanoparticles showed pH and reactive oxygen species (ROS)-triggered drug release behavior. In vitro cell experiments revealed that the blank nanoparticles were completely nontoxic to cultured cells, and the curcumin-loaded nanoparticles exhibited efficient antitumor efficiency against cancer cells. Moreover, the drug-loaded nanoparticles performed an enhanced growth inhibition in three-dimensional multicellular tumor spheroids. Thus, these nanocarriers would be a promising candidate for curcumin delivery in tumor treatment.

Topics: Biocompatible Materials; Boronic Acids; Cell Proliferation; Cell Survival; Chitosan; Curcumin; Drug Carriers; Drug Liberation; Hep G2 Cells; Humans; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Metal Nanoparticles; Nanoparticles; Nanotechnology; Reactive Oxygen Species; Spheroids, Cellular

Curcumin (Cur) has a wide range of bioactivities that show potential for the treatment of cancer as well as chronic diseases associated with inflammation and aging. However, the therapeutic efficacy of Cur has been hampered by its rapid degradation under physiological conditions and low aqueous solubility. To address these problems, we prepared Cur-loaded polymeric nanoparticles (CNPs), in which Cur was complexed with phenylboronic acid-containing framboidal nanoparticles (NPs), by simple mixing of Cur and NPs in an aqueous solution. CNPs showed improved chemical stability of Cur and released it in a sustained manner under physiological conditions. Furthermore, CNPs significantly enhanced the antiangiogenic and anticancer activities of Cur in chicken chorioallantoic membrane models.

Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Boronic Acids; Curcumin; HT29 Cells; Human Umbilical Vein Endothelial Cells; Humans; Nanoparticles