pH and reduction dual-responsive micelles based on novel polyurethanes with detachable poly(2-ethyl-2-oxazoline) shell for controlled release of doxorubicin

Drug Deliv. 2019 Dec;26(1):300-308. doi: 10.1080/10717544.2019.1580323.

Abstract

We describe a biodegradable amphiphilic polyurethane (PU) with disulfide bonds in the main chain [PEtOz-b-PU(SS)-b-PEtOz]. This multi-block PU was synthesized using poly (ε-caprolactone) diol (PCL-SS-PCL) and poly (2-ethyl-2-oxazoline) (PEtOz-OH) as soft segments, and bis (2-isocyanatoethyl) disulfide as the hard segment. Acid-sensitive PEtOz-OH was used as a hydrophilic segment for pH sensitivity. And reduction sensitivity was induced via disulfide bonds incorporated into the hydrophobic poly (ε-caprolactone) segment of the amphiphilic PUs. The system can self-assemble to form micelles responsive to pH and reducing conditions. The properties of the micelle were studied with dynamic light scattering and scanning electron microscopy. Doxorubicin (DOX) was chosen as a model drug. The in vitro release studies showed that PEtOz-b-PU(SS)-b-PEtOz micelle could degrade more rapidly and completely in a reductive and acidic environment [10 mM dl-Dithiothreitol, pH 5.0]. The methyl tetrazolium (MTT) assay and fluorescent microscopy confirmed the cytotoxicity of the DOX-loaded micelles. This work provides a promising dual-responsive drug carrier based on amphiphilic PU to achieve efficient drug delivery.

Keywords: Polyurethane; drug delivery; dual- responsive; micelle; poly(2-ethyl-2-oxazoline).

MeSH terms

  • Caproates / chemistry
  • Delayed-Action Preparations / chemistry*
  • Doxorubicin / chemistry*
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Hydrogen-Ion Concentration
  • Lactones / chemistry
  • Micelles
  • Particle Size
  • Polyamines / chemistry*
  • Polymers / chemistry
  • Polyurethanes / chemistry*

Substances

  • Caproates
  • Delayed-Action Preparations
  • Drug Carriers
  • Lactones
  • Micelles
  • Polyamines
  • Polymers
  • Polyurethanes
  • poly(2-ethyl-2-oxazoline)
  • caprolactone
  • Doxorubicin

Grants and funding

This work is financially supported by National Natural Science Foundation of China (No. 51802127 and 81871805) and grants from Xuzhou Basic Research Program of Jiangsu Province (NO. KC16SG256), Graduate Scientific Research Innovation Program of Jiangsu Province (NO. KYCX17-1581 and NO. KYCX18-2112) and PAPD of Jiangsu Province.