Polymer Nanogels as Reservoirs to Inhibit Hydrophobic Drug Crystallization

Ziang Li, Nicholas J. Van Zee, Frank S. Bates, Timothy P Lodge

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The effects of cross-link density and composition on the loading and in vitro dissolution of the drug phenytoin as amorphous solid dispersions in emulsion polymerized poly(N-isopropylacrylamide) (PNIPAm) and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) nanogels were investigated near the lower critical solution temperature (LCST). Nanogel size and particle density in phosphate buffered saline were quantified by dynamic light scattering (DLS) and viscometry experiments, while drug-nanogel interactions were revealed by cross peaks in aqueous-state nuclear Overhauser effect spectroscopy measurements. Spray-dried dispersions (SDDs) of drug-loaded PNIPAm nanogel particles (R ≈ 43 nm) were directly visualized by cryogenic transmission electron microscopy and further quantified by small-angle X-ray scattering during in vitro dissolution. SDD dissolution profiles were highly dependent on the nanogel cross-link density and directly correlated with the state of dispersion of the drug-loaded nanogel particles. A balance between net particle hydrophobicity and hydrophilicity along with the distance in temperature from the LCST are shown to dictate the in vitro dissolution of the amorphous solid dispersions. Solubility enhancement mechanisms disclosed in this study provide essential guidance for the design of effective nanogels for oral drug delivery applications.

Original languageEnglish (US)
Pages (from-to)1232-1243
Number of pages12
JournalACS nano
Volume13
Issue number2
DOIs
StatePublished - Feb 26 2019

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Crystallization
Dispersions
Polymers
Dissolution
drugs
crystallization
dissolving
polymers
Pharmaceutical Preparations
Drug interactions
sprayers
Viscosity measurement
Hydrophilicity
Overhauser effect
Dynamic light scattering
viscometry
Hydrophobicity
X ray scattering
Drug delivery
Cryogenics

Keywords

  • cryo-TEM
  • drug delivery
  • lower critical solution temperature
  • N-isopropylacrylamide
  • nanogel
  • nanoparticle

How much support was provided by MRSEC?

  • Shared

Reporting period for MRSEC

  • Period 6

PubMed: MeSH publication types

  • Journal Article

Cite this

Polymer Nanogels as Reservoirs to Inhibit Hydrophobic Drug Crystallization. / Li, Ziang; Van Zee, Nicholas J.; Bates, Frank S.; Lodge, Timothy P.

In: ACS nano, Vol. 13, No. 2, 26.02.2019, p. 1232-1243.

Research output: Contribution to journalArticle

Li, Ziang ; Van Zee, Nicholas J. ; Bates, Frank S. ; Lodge, Timothy P. / Polymer Nanogels as Reservoirs to Inhibit Hydrophobic Drug Crystallization. In: ACS nano. 2019 ; Vol. 13, No. 2. pp. 1232-1243.
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