Novel hydrophobin-coated docetaxel nanoparticles for intravenous delivery: in vitro characteristics and in vivo performance

Abstract

Novel hydrophobin (H star Protein® B, HPB)-coated docetaxel (DTX) nanoparticles were designed for intravenous delivery. DTX-HPB nanoparticles (DTX-HPB-NPs) were prepared using a nanoprecipitation-ultrasonication technique. The physicochemical properties in terms of particle size, size distribution, zeta potential, morphology, crystalline state of the drug, in vitro release and plasma stability were evaluated. To investigate the drug-hydrophobin interaction, FTIR analysis was carried out. The pharmacokinetics of DTX-HPB-NPs and Taxotere were compared after i.v. administration to rats. The optimized formulations have a high drug loading (>25%) and nanoparticle yield (>93%), small particle size with a narrow distribution, and exhibit delayed release. X-ray diffraction (XRD) demonstrated that the drug is present in a crystalline state. FTIR analysis suggested that the interaction of DTX and HPB involved hydrogen bonding. In vitro hemolysis study confirmed the safety of these nanoparticles. In plasma, DTX-HPB nanoparticles exhibited a significantly enhanced Cmax (1300.618±405.045 ng/mL vs 453.174±164.437 ng/mL, p<0.05), and AUC0-t (409.602±70.267 vs 314.924±57.426 μg/Lh, p<0.05), and a significantly reduced volume of distribution (36.635±15.189 vs 95.199±40.972 L/kg, p<0.05) compared with the Taxotere. These results demonstrated that hydrophobin has the potential to be used as a novel biocompatible biomaterial for drug delivery.

Keywords: Acetonitrile (PubChem CID: 6342); Docetaxel; Docetaxel (PubChem CID: 148124); Drug delivery; Formic acid (PubChem CID: 284); Hydrophobin; Methanol (PubChem CID: 887); Nanoparticles; Paclitaxel (PubChem CID: 36314); Ter-Butyl methyl ether (PubChem CID: 15413); Tween 80 (PubChem CID: 6364656).