Abstract

Herein, a new process to manufacture multicore micelles nanoparticles reinforced with co-assembly via hydrophobic interaction and electrostatic interaction under the help of ultrasonication was developed. The precise co-assembly between negative/hydrophobic drug and positive charged amphiphilic copolymer based pluronic platform allows the formation of complex micelles structures as the multicore motif with predefined functions. In this study, curcumin was selected as a drug model while positively charged copolymer was based on a pluronic-conjugated gelatin with different hydrophobicity length of Pluronic F87 and Pluronic F127. Under impact of dual hydrophobic and electrostatic interactions, the nCur-encapsulated core–shell micelles formed ranging from 40 nm to 70 nm and 40–100 nm by transmission electron microscopy (TEM) and Dynamic Light Scattering (DLS), respectively. It is found that the structures emerged depended on the relative lengths of the hydrophobic blocks in pluronic. Regarding g2(τ) behavior from DLS measurement, the nanogels showed a high stability in spherical form. Surprisingly, the release profiles showed a sustainable behavior of Cur from this system for drug delivery approaches. In vitro study exhibited that nCur-encapsulated complex micelles increased inhibitory activity against cancer cells growth with IC50 is 4.02 ± 0.11 mg/L (10.92 ± 0.3 µM) which is higher than of free curcumin at 9.40 ± 0.17 mg/L (25.54 ± 0.18 µM). The results obtained can provide the new method to generate the hierarchical assembly of copolymers with incorporated loading with the same property.

Highlights

  • Hierarchical assembly of the amphiphilic block copolymer, which allows the directly tailor and structure the nanoscale micelles ordered organization has recently drawn great research interest [1,2,3,4].The emergence of micelle packing with well-design at the higher level complex formulation, which comes from the approaching the concept of biological macromolecules as protein, have proven to be an excellent candidate in drug delivery system field of amphiphilic block copolymer [5,6]

  • The synthetic route to the amphiphilic gelatin copolymer (GP) was performed by a grafting to method, in which hydroxyl groups of Pluronic was first modified with p-NPC to make possible coupling reaction between Pluronic and the amine groups (-NH2 ) on gelatin backbone, as similar with our previous study [46]

  • The results indicated that the introduction gelatin leads that the introduction of gelatin leads to the superiority of hydrophilic segments for which the critical micellization concentration (CMC)

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Summary

Introduction

Hierarchical assembly of the amphiphilic block copolymer, which allows the directly tailor and structure the nanoscale micelles ordered organization has recently drawn great research interest [1,2,3,4]. The emergence of micelle packing with well-design at the higher level complex formulation, which comes from the approaching the concept of biological macromolecules as protein, have proven to be an excellent candidate in drug delivery system field of amphiphilic block copolymer [5,6]. We have developed several approaches to obtain complex self-assemblies of amphiphilic block copolymer [4,8], in which specific interactions, mainly hydrophobic–hydrophobic interactions connect the core and shell. The formation of micelles by complexation of hydrophilic segments with drug counterions, and their cargo structure with the standard interface via hydrophobic–hydrophobic interaction propose the system with such a core packing motif which have attracted significant interest for applications in materials chemistry [15,16]

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