Novel Redox-Responsive Amphiphilic Copolymer Micelles for Drug Delivery: Synthesis and Characterization

Abstract

Abstract. A novel redox-responsive amphiphilic polymer was synthesized with bioreductive trimethyllocked quinone propionic acid for a potential triggered drug delivery application. The aim of this study was to synthesize and characterize the redox-responsive amphiphilic block copolymer micelles containing pendant bioreductive quinone propionic acid (QPA) switches. The redox-responsive hydrophobic block (polyQPA), synthesized from QPA-serinol and adipoyl chloride, was end-capped with methoxy poly(ethylene glycol) of molecular weight 750 (mPEG 750 ) to achieve a redox-responsive amphiphilic block copolymer, polyQPA-mPEG 750 . PolyQPA-mPEG 750 was able to self-assemble as micelles to show a critical micelle concentration (CMC) of 0.039%w/v (0.39 mg/ml, 0.107 mM) determined by a dye solubilization method using 1,6-diphenyl-1,3,5-hexatriene (DPH) in phosphate-buffered saline (PBS). The mean diameter of polymeric micelles was found to be 27.50 nm (PI=0.064) by dynamic light scattering. Furthermore, redox-triggered destabilization of the polymeric micelles was confirmed by 1 H-NMR spectroscopy and particle size measurements in a simulated redox state. PolyQPA-mPEG 750 underwent triggered reduction to shed pendant redox-responsive QPA groups and its polymeric micelles were swollen to be dissembled in the presence of a reducing agent, thereby enabling the release of loaded model drug, paclitaxel. The redox-responsive polyQPA-mPEG 750 polymer micelles would be useful as a drug delivery system allowing triggered drug release in an altered redox state such as tumor microenvironments with an altered redox potential and/or redox enzyme upregulation.

Synthesis and Technology of Nanoemulsion-Based Pesticide Formulation

“…CMC value is a point at which self-assembly occurs and the addition of surfactant after this point is no longer reduces the surface tension. Several techniques have been used in revealing the CMC value such as fluorescence probe [84], surface plasmon resonance [85], dye solubilization [86], tensiometer [87], viscometry [88], calorimetry [89] and electrical conductivity [90].…”

Novel Biodegradable Polymer with Redox‐Triggered Backbone Cleavage Through Sequential 1,6‐Elimination and 1,5‐Cyclization Reactions

“…As explained in those studies, the trend may be explained by the solubility reversal of the polymer core's hydrophobic nature into hydrophilic nature, due to successful unmasking of amine group in its backbone. [1a,17] The consequent hydration of the particles induced drastic swelling, which can be correlated with observed particle size increase.…”

“…Over the past two decades, significant progress has been made toward the development of synthetic biodegradable polymers for advanced biomedical applications such as tissue regeneration and controlled drug delivery . A number of biodegradable polymers could be engineered using various approaches to apply biocompatible materials into platform design.…”

Cancer drug delivery in the nano era: An overview and perspectives

“…Integrin-binding sequence peptides with covalent bonds to the micelle can actively target tumors ( 101 ). Block copolymers are environmental response modifiers that display a physico-chemical response to stimuli such as temperature ( 102 – 104 ), pH ( 105 ), light ( 106 ), or electricity ( 107 ). Some block copolymers can produce functional signals and higher levels of signaling ( 103 , 108 ); thus, micelles made from them are called ‘intelligent’ block copolymer micelles.…”