pH‐ and β‐cyclodextrin‐responsive micelles based on polyaspartamide derivatives as drug carrier

Abstract

A novel kind of graft polymer poly(aspartic acid)-ethanediamine-g-adamantane/methyloxy polyethylene glycol (Pasp-EDA-g-Ad/mPEG) was designed and synthesized for drug delivery in this study. The chemical structure of the prepared polymer was confirmed by proton NMR. The obtained polymer can self-assemble into micelles which were stable under a physiological environment and displayed pH-and bcyclodextrin (b-CD)-responsive behaviors because of the acidlabile benzoic imine linkage and hydrophobic adamantine groups in the side chains of the polymer. The doxorubicin (Dox)-loaded micelles showed a slow release under physiological conditions and a rapid release after exposure to weakly acidic or b-CD environment. The in vitro cytotoxicity results suggested that the polymer was good at biocompatibility and could remain Dox biologically active. Hence, the Pasp-EDA-gAd/mPEG micelles may be applied as promising controlled drug delivery system for hydrophobic antitumor drugs. V C 2015

Benzoic‐Imine‐Based Physiological‐pH‐Responsive Materials for Biomedical Applications

“…The polymer formed micelles at physiological pH value after complexation with β‐cyclodextrin (β‐CD), which contained a hydrophobic microdomain. On decreasing the pH value from 7.4 to 6.3, an abrupt change in micelle size was observed from 220 to 25 nm, accompanied by surface‐charge conversion, owing to disintegration and reorganization of the micelles, mediated by the change in chemical structure, that is, cleavage of the benzoic imine moiety, which facilitated the cell–micelle interactions . At pH≈5, the aggregates completely disintegrated, which accelerated drug release inside the cells.…”

Stimuli-Responsive Poly(aspartamide) Derivatives and Their Applications as Drug Carriers

“…Another strategy for preparing pH-responsive polymers is to introduce pH-cleavable linkages, which mainly include hydrazone [60][61][62], imine [63], acetal, orthoester and 2,3dialkylmaleamidic amide linkages. Hydrazone linkage [64] plays an important role in the preparation of pH-responsive polymers.…”

A dual pH- and reduction-responsive anticancer drug delivery system based on PEG–SS–poly(amino acid) block copolymer

“…In the past few decades, more and more attention has been drawn to nano-sized drug or gene delivery systems, such as nanogels, nanoparticles and micelles, [1][2][3][4][5][6][7][8][9][10][11][12][13] due to their prolonged retention time, lower toxicity to normal cells, admirable biodegradability, and improved drug accumulation via the enhanced permeability and retention (EPR) effect. 14 Micelles, in particular, are widely utilized in research on anticancer drug nanocarriers due to their unique core-shell structures in which drugs are stably encapsulated in the 'core' and are difficult to be captured by the reticuloendothelial system (RES) undesirably during delivery to the targeted tumor site.…”

“…14 Micelles, in particular, are widely utilized in research on anticancer drug nanocarriers due to their unique core-shell structures in which drugs are stably encapsulated in the 'core' and are difficult to be captured by the reticuloendothelial system (RES) undesirably during delivery to the targeted tumor site. Moreover, micelles are capable of releasing drugs in response to various internal and/or external stimuli such as temperature, 7 pH, 5,15,16 redox substances, 1,15,17,18 ultrasound, 19 and light; 20 thus increasing interests have been garnered with the in-depth study of the features of tumor microenvironment, e.g. decreased pH value, increased temperature and enriched reduction substances.…”