Effect of ultrasonication on self-assembled nanostructures formed by amphiphilic positive-charged copolymers and negative-charged drug

Abstract

Self-assembly of the amphiphilic copolymer into core-shell-like nanoparticles is the new tactic to tailor carriers toward rationalization in the field of drug-delivery systems. Herein, a facile route for examining how the entrapment of a hydrophobic and negative-charge drug affects the micellar structure of a positive-charged copolymer and its biological behavior was developed. In this study, Pluronic F127-grafted chitosan (CF127) was utilized as a positive-charged copolymer for in situ loading of nanocurcumin in a cosolvent condition. Ultrasonication was found to be an effective method to control the self-assembly of phosphocasein and its interaction with curcumin. The superstructure of the incorporated nanoparticles was fabricated in the medium under unimolecular micelles as vesicular structure (SV) at lower ultrasonic condition while large complex micelles (multimicelle aggregates, LCMs) at higher ultrasonic power density. According to transmission electron microscopy, variable UV-visible spectrophotometry, as well as fluorescence spectroscopy, nanocurcumin was not only incorporated into the hydrophobic micelle cores via hydrophobic interaction but also underwent electrostatic interaction with amine groups on chitosan backbone, resulting in micellar aggregation and finally turning in LCMs. Furthermore, regarding dynamic light scattering measurements, correlation coefficients of SV, as well as LCMs, were higher than 0.9, which means that all nanostructures were homogeneous in size under precise control by ultrasonication. Cell-culture studies showed that both unique morphologies endowed fibroblast cell development. Interestingly, the more complex structure as LCM exhibited as a potential candidate in cancer therapy. These corollaries suggest that the morphology of micelles based on cationic amphiphilic block copolymer can be modulated by adding negative-charged/hydrophobic molecules under varying condition of ultrasonication that reinforces their prospective applications as nanocarriers for drug-delivery systems.