Acid-labile core cross-linked micelles for pH-triggered release of antitumor drugs.

Centre for Advanced Macromolecular Design, The University of New South Wales, Sydney 2052, NSW, Australia.
Biomacromolecules (Impact Factor: 5.79). 08/2008; 9(7):1826-36. DOI: 10.1021/bm800043n
Source: PubMed

ABSTRACT Micelles of a model amphiphilic block copolymer, poly(hydroxyethyl acrylate)-block-poly(n-butyl acrylate) (PHEA-b-PBA), synthesized via the RAFT polymerization were cross-linked by copolymerization of a degradable cross-linker from the living RAFT-end groups of PBA chains, yielding a cross-linked core without affecting significantly the original micelle size. The cross-linker incorporation into the micelles was evidenced via physicochemical analysis of the copolymer unimers formed upon acidic cleavage of the cross-linked micelles. High doxorubicin loading capacities (60 wt %) were obtained. Hydrolysis of less than half of the cross-links in the core was found to be sufficient to release doxorubicin faster at acidic pH compared to neutral pH. The system represents the first example of core-cross-linked micelles that can be destabilized (potentially both above and below CMC) by the pH-dependent cleavage of the cross-links and the subsequent polarity change in the core to enable the release of hydrophobic drugs entrapped inside the micelle.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Well-defined amphiphilic block copolymers composed of hydrophilic and hydrophobic blocks linked through an acid-labile acetal bond were synthesized directly by RAFT polymerization using a new poly(ethylene glycol) (PEG) macroRAFT agent modified with an acid-labile group at its R-terminal. The new macroRAFT agent was used for polymerization of poly(t-butyl methacrylate) (PtBMA) or poly(cholesterol-methacrylate) (PCMA) to synthesize well-defined block copolymers with a PEG block sheddable under acidic conditions. The chain extension polymerization kinetics showed known traits of RAFT polymerization. The molecular weight distributions of the copolymers prepared using the new macroRAFT agent remained below 1.2 during the polymerizations and the molecular weight of the copolymers was linearly proportional to monomer conversions. The acidcatalyzed hydrolysis behavior of the PEG-macroRAFT agent and the PEG-b-PtBMA (Mn = 13,600 by GPC, PDI = 1.10) was studied by GPC, H-1 NMR and UV-vis spectroscopy. The half-life of acid-hydrolysis was 70 min at pH 2.2 and 92 h at pH 4.0. The potential use of the pH-labile shedding behavior of the copolymers was demonstrated by conjugating a thiol-modified siRNA to omega-pyridyldisulfide modified PEG-b-PCMA. The resultant PEG-b-PCMA-b-siRNA triblock modular polymer released PCMA-b-siRNA segment in acidic and siRNA segment in reductive conditions, as confirmed by polyacrylamide gel electrophoresis.
    European Polymer Journal 10/2013; 49(10):2895-2905. DOI:10.1016/j.eurpolymj.2013.03.036 · 3.24 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nanographite oxide prepared by a chemical oxidation method was characterized by SEM, XRD, FT-IR, zeta potential and BET surface area. The use of nanographite oxide as an adsorbent to remove p-nitrophenol from aqueous solutions was investigated. Adsorption experiments were carried out as a function of the contact time, initial p-nitrophenol concentration, pH, adsorbent dosage, and temperature. It was found that the nanographite oxide possessed a large surface area and was particularly effective for the removal of p-nitrophenol. The removal efficiency of p-nitrophenol decreased with an increase of the solution pH from 4.0 to 7.0 and an increase in the temperature. The adsorption of p-nitrophenol onto nanographite oxide reached equilibrium within 2 h. The maximum adsorption capacity of nanographite oxide for p-nitrophenol was 268.5 mg/g at 283 K and a natural pH. The Freundlich isotherm was the best choice to describe the adsorption behavior. The kinetic data were presented by the pseudo-second-order kinetic model. The parameters suggested that the adsorption process of p-nitrophenol onto nanographite oxide occurred via physisorption process and was exothermic in nature. Hydrogen-bonding, electron donor–acceptor and Lewis acid/base interactions were the main mechanisms affecting the adsorption capacity, while dispersive interactions were also found to influence the adsorption of p-nitrophenol through the influence of its deactivating functional groups on the aromatic ring. The results showed that nanographite oxide can be used as a new adsorbent which has higher adsorption capacity and faster adsorption rate for the removal of p-nitrophenol.
    Colloids and Surfaces A Physicochemical and Engineering Aspects 10/2014; DOI:10.1016/j.colsurfa.2014.10.020 · 2.35 Impact Factor


Available from
May 21, 2014