Polymersomes from dual responsive block copolymers: drug encapsulation by heating and acid-triggered release

Biomacromolecules. 2013 May 13;14(5):1555-63. doi: 10.1021/bm400180n. Epub 2013 Apr 18.

Abstract

A series of well-defined thermoresponsive diblock copolymers (PEO45-b-PtNEAn, n=22, 44, 63, 91, 172) were prepared by the atom transfer radical polymerization of trans-N-(2-ethoxy-1,3-dioxan-5-yl) acrylamide (tNEA) using a poly(ethylene oxide) (PEO45) macroinitiator. All copolymers are water-soluble at low temperature, but upon quickly heating to 37 °C, laser light scattering (LLS) and transmission electron microscopy (TEM) characterizations indicate that these copolymers self-assemble into aggregates with different morphologies depending on the chain length of PtNEA and the polymer concentration; the morphologies gradually evolved from spherical solid nanoparticles to a polymersome as the degree of polymerization ("n") of PtNEA block increased from 22 to 172, with the formation of clusters with rod-like structure at the intermediate PtNEA length. Both the spherical nanoparticle and the polymersome are stable at physiological pH but susceptible to the mildly acidic medium. Acid-triggered hydrolysis behaviors of the aggregates were investigated by LLS, Nile red fluorescence, TEM, and (1)H NMR spectroscopy. The results revealed that the spherical nanoparticles formed from PEO45-b-PtNEA44 dissociated faster than the polymersomes of PEO45-b-PtNEA172, and both aggregates showed an enhanced hydrolysis under acidic conditions. Both the spherical nanoparticle and polymersome are able to efficiently load the hydrophobic doxorubicin (DOX), and water-soluble fluorescein isothiocyanate-lysozyme (FITC-Lys) can be conveniently encapsulated into the polymersome without using any organic solvent. Moreover, FITC-Lys and DOX could be coloaded in the polymersome. The drugs loaded either in the polymersome or in the spherical nanoparticle could be released by acid triggering. Finally, the DOX-loaded assemblies display concentration-dependent cytotoxicity to HepG2 cells, while the copolymers themselves are nontoxic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins / chemical synthesis*
  • Acrylic Resins / pharmacology
  • Cell Survival / drug effects
  • Doxorubicin / pharmacology
  • Drug Carriers / chemical synthesis*
  • Drug Carriers / pharmacology
  • Drug Compounding
  • Fluorescein-5-isothiocyanate
  • Hep G2 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Hydrophobic and Hydrophilic Interactions
  • Micelles
  • Microscopy, Electron, Transmission
  • Muramidase
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Particle Size
  • Polymerization
  • Polymers / chemical synthesis*
  • Polymers / pharmacology
  • Solubility
  • Temperature

Substances

  • Acrylic Resins
  • Drug Carriers
  • Micelles
  • Polymers
  • Doxorubicin
  • Muramidase
  • Fluorescein-5-isothiocyanate