Arylsulfatase A bound to poly(butyl cyanoacrylate) nanoparticles for enzyme replacement therapy--physicochemical evaluation

Pharmazie. 2014 Jul;69(7):518-24.

Abstract

Arylsulfatase A (ASA) deficiency is the cause of metachromatic leucodystrophy (MLD), a lysosomal storage disease associated with severe neurological disorders. Poly(butyl cyanoacrylate) (PBCA) nanoparticles overcoated with polysorbate 80 enabled the delivery of several drugs across the blood-brain barrier to the brain suggesting that these nanoparticles also may transport ASA across this barrier. The objective of this research, therefore, was to evaluate the feasibility of loading ASA onto PBCA nanoparticles. A stable ASA-loaded PBCA nanoparticle formulation was developed that could be easily freeze-dried and stored over a period of more than 8 weeks. The maximum loading capacity for this enzyme was -59 microg per 1 mg of PBCA. In the presence of 3% sucrose as a lyoprotector the activity of freeze-dried ASA was found to be 100% recoverable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catechols
  • Cerebroside-Sulfatase / administration & dosage
  • Cerebroside-Sulfatase / chemistry
  • Cerebroside-Sulfatase / therapeutic use*
  • Chromatography, Gas
  • Chromatography, Gel
  • Drug Carriers
  • Drug Compounding
  • Electrochemistry
  • Enbucrilate / chemistry*
  • Enzyme Replacement Therapy / methods*
  • Excipients
  • Freeze Drying
  • Indicators and Reagents
  • Kinetics
  • Nanoparticles
  • Protein Binding
  • Solubility
  • Surface Properties
  • Tissue Adhesives

Substances

  • Catechols
  • Drug Carriers
  • Excipients
  • Indicators and Reagents
  • Tissue Adhesives
  • Cerebroside-Sulfatase
  • Enbucrilate
  • 4-nitrocatechol sulfate