Denatured protein-coated docetaxel nanoparticles: Alterable drug state and cytosolic delivery

Abstract

Many lead compounds have a low solubility in water, which substantially hinders their clinical application. Nanosuspensions have been considered a promising strategy for the delivery of water-insoluble drugs. Here, denatured soy protein isolate (SPI)-coated docetaxel nanosuspensions (DTX-NS) were developed using an anti-solvent precipitation-ultrasonication method to improve the water-solubility of DTX, thus improving its intracellular delivery. DTX-NS, with a diameter of 150-250nm and drug-loading up to 18.18%, were successfully prepared by coating drug particles with SPI. Interestingly, the drug state of DTX-NS was alterable. Amorphous drug nanoparticles were obtained at low drug-loading, whereas at a high drug-loading, the DTX-NS drug was mainly present in the crystalline state. Moreover, DTX-NS could be internalized at high levels by cancer cells and enter the cytosol by lysosomal escape, enhancing cell cytotoxicity and apoptosis compared with free DTX. Taken together, denatured SPI has a strong stabilization effect on nanosuspensions, and the drug state in SPI-coated nanosuspensions is alterable by changing the drug-loading. Moreover, DTX-NS could achieve cytosolic delivery, generating enhanced cell cytotoxicity against cancer cells.

Keywords: 4′,6-Diamidino-2-phenylindole (PubChem CID: 160166); 5-Diphenyltetrazolium bromide (PubChem CID: 64965); Cellular uptake; Chlorpromazine (PubChem CID: 2726); Cytosolic delivery; Dimethyl sulfoxide (PubChem CID: 679); Docetaxel; Docetaxel (PubChem CID: 148124); Fluorescein isothiocyanate (PubChem CID: 18730); Nanosuspensions; Rhodamine B isothiocyanate (PubChem CID: 6455488); Soy protein isolate; Trehalose (PubChem CID: 7427); Tween-80 (PubChem CID: 5281955); nystatin (PubChem CID: 6433272).