Honokiol nanoparticles stabilized by oligoethylene glycols codendrimer: in vitro and in vivo investigations

Nanoparticles based on dendrimers were explored as excellent candidates for nanoscale drug delivery system. In this study, the fluorescently labeled amphiphilic codendrimer PGC from PAMAM G4.0 and oligoethylene glycol dendron was utilized as a carrier to prepare honokiol-loaded nanoparticles (HK NPs) via an evaporation method augmented by ultrasonication with an optimized drug-loading content (∼60%, wt%). The release of HK NPs showed a sustained release manner and was completed within 120 h. The HK NPs presented higher cytotoxicity against 4T1 cells, and the cellular uptake mechanism was proven to be caveolae-mediated endocytosis and clathrin-mediated endocytosis. Importantly, the HK NPs resulted in a strong antitumor efficacy on the 4T1 breast tumor model in vivo, and no significant adverse effects were observed. In addition, in vivo studies also showed that the HK NPs possessed better tumor accumulation over HCPT injection. According to the higher drug-loading content, enhanced antitumor efficacy, and appropriate particle size, HK NPs were shown to be safe and efficient drug delivery systems and could have potential application in cancer chemotherapy.