Preparation, characterization and evaluation of HPβCD-PTX/PHB nanoparticles for pH-responsive, cytotoxic and apoptotic properties

Int J Biol Macromol. 2024 May 9;270(Pt 2):132268. doi: 10.1016/j.ijbiomac.2024.132268. Online ahead of print.

Abstract

Paclitaxel (PTX) is a potent anticancer drug. However, PTX exhibits extremely poor solubility in aqueous solution along with severe side effects. Therefore, in this study, an inclusion complex was prepared between PTX and hydroxypropyl-β-cyclodextrin (HPβCD) by solvent evaporation to enhance the drug's solubility. The HPβCD-PTX inclusion complex was then encapsulated in poly-3-hydroxybutyrate (PHB) to fabricate drug-loaded nanoparticles (HPβCD-PTX/PHB NPs) by nanoprecipitation. The HPβCD-PTX/PHB NPs depicted a higher release of PTX at pH 5.5 thus demonstrating a pH-dependent release profile. The cytotoxic properties of HPβCD-PTX/PHB NPs were tested against MCF-7, MDA-MB-231 and SW-620 cell lines. The cytotoxic potential of HPβCD-PTX/PHB NPs was 2.59-fold improved in MCF-7 cells in comparison to free PTX. Additionally, the HPβCD-PTX/PHB NPs improved the antimitotic (1.68-fold) and apoptotic (8.45-fold) effects of PTX in MCF-7 cells in comparison to PTX alone. In summary, these pH-responsive nanoparticles could be prospective carriers for enhancing the cytotoxic properties of PTX for the treatment of breast cancer.

Keywords: HPβCD-drug inclusion complex; Nano-system; PHB; Paclitaxel.