Co-Encapsulation of Paclitaxel and JQ1 in Zein Nanoparticles as Potential Innovative Nanomedicine

Abstract

The manuscript describes the development of zein nanoparticles containing paclitaxel (PTX) and the bromo-and extra-terminal domain inhibitor (S)-tertbutyl2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepin-6-yl)acetate (JQ1) together with their cytotoxicity on triple-negative breast cancer cells. The rationale of this association is that of exploiting different types of cancer cells as targets in order to obtain increased pharmacological activity with respect to that exerted by the single agents. Zein, a protein found in the endosperm of corn, was used as a biomaterial to obtain multidrug carriers characterized by mean sizes of ˂200 nm, a low polydispersity index (0.1–0.2) and a negative surface charge. An entrapment efficiency of ~35% of both the drugs was obtained when 0.3 mg/mL of the active compounds were used during the nanoprecipitation procedure. No adverse phenomena such as sedimentation, macro-aggregation or flocculation occurred when the nanosystems were heated to 37 °C. The multidrug nanoformulation demonstrated significant in vitro cytototoxic activity against MDA-MB-157 and MDA-MB-231 cancer cells by MTT-test and adhesion assay which was stronger than that of the compounds encapsulated as single agents. The results evidence the potential application of zein nanoparticles containing PTX and JQ1 as a novel nanomedicine.

BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications

“…The synergistic anticancer effect was associated with the inhibition of autophagy and potentiation of apoptosis [ 132 ]. Fueled by the synergistic combination effect of paclitaxel and JQ1, a novel nanoparticle-based formulation has been developed to encapsulate both drugs together in Zein nanoparticles [ 133 ]. This novel nanoformulation was reported to exhibit a superior anticancer effect to either drug alone in triple-negative breast cancer cells in vitro [ 133 ].…”

Case Study in the Application of OnePot Prototype Reactor for the Scale-Up of Protein-Based Nanoparticle Production

“…It is a low-cost biomaterial, insoluble in water yet soluble in organic solvents, such as ethanol, acetone, or acetyl acetone. Due to its versatility, it has been widely employed in the development of micro/nanoparticles, gels, film, and scaffolds with the aim of entrapping both hydrophilic and hydrophobic molecules. − Various preparation approaches have been proposed to obtain zein nanoparticles, with cross-linking, nanoprecipitation, coacervation, and micromixing being the most commonly used techniques. − However, these methods are typically carried out on a small scale and are characterized by batch-to-batch variability. The translation of these procedures into a scaling-up process can be challenging because it is usually hard to obtain large amounts of nanosystems having the same characteristics as a lab-scale batch. − …”