Loading and distribution of a model small molecule drug in poly(N-isopropylacrylamide) brushes: a neutron reflectometry and AFM study

Langmuir. 2013 Mar 12;29(10):3259-68. doi: 10.1021/la305088k. Epub 2013 Feb 27.

Abstract

The structure of a hydrated poly(N-isopropylacrylamide) brush loaded with 5 vol % Isoniazid is studied as a function of temperature using neutron reflectometry (NR) and atomic force microscopy (AFM). NR measurements show that Isoniazid increases the thickness of the brush before, during and after the polymer collapse, and it is retained inside the brush at all measured temperatures. The Isoniazid concentration in the expanded brush is ~14% higher than in the bulk solution, and the concentration nearly doubles in the collapsed polymer, suggesting stronger binding between Isoniazid and the polymer compared to water, even at temperatures below the lower critical solution temperature (LCST) where the polymer is hydrophilic. Typically, additives that bind strongly to the polymer backbone and increase the hydrophilicity of the polymer will delay the onset of the LCST, which is suggested by AFM and NR measurements. The extent of small-molecule loading and distribution throughout a thermo-responsive polymer brush, such as pNIPAAm, will have important consequences for applications such as drug delivery and gating.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acrylamides / chemistry*
  • Acrylic Resins
  • Drug Carriers / chemistry
  • Isoniazid / chemistry
  • Microscopy, Atomic Force / methods*
  • Polymers / chemistry*

Substances

  • Acrylamides
  • Acrylic Resins
  • Drug Carriers
  • Polymers
  • poly-N-isopropylacrylamide
  • Isoniazid