Near-infrared light-responsive, pramipexole-loaded biodegradable PLGA microspheres for therapeutic use in Parkinson's disease

Eur J Pharm Biopharm. 2019 Aug:141:1-11. doi: 10.1016/j.ejpb.2019.05.013. Epub 2019 May 14.

Abstract

Parkinson's disease (PD) is associated with symptoms such as tremor and bradykinesia which, together with a rigorous dosing regimen, can place an untenable burden on patients. These issues underscore the need for triggerable, modulated drug delivery systems. Currently, pramipexole (PRX) is the most widely used non-ergot dopamine agonist for the treatment of PD. In this study, near-infrared light-responsive PRX and hollow gold nanospheres (HGNS)-loaded biodegradable poly (D, L-lactide-co-glycolide) (PLGA) microspheres (PRX/HGNS MS) were fabricated using solid-in-oil-in-water (S/O/W) and water-in-oil-in-water (W/O/W) emulsion-solvent evaporation techniques to achieve modulated drug release. The PRX/HGNS MS were uniform, with an average diameter of approximately 24 µm, favorable PRX and HGNS encapsulation efficiencies (51.71 ± 0.54% and 65.15 ± 2.30%, respectively) and rapid, controllable drug release both in vitro and in vivo. Cytotoxicity tests revealed no significant differences between HGNS and PRX/HGNS MS when compared with a negative control. Pharmacodynamics and immunohistochemistry studies revealed a more rapid recovery of striatum in the group treated with PRX/HGNS MS produced using the S/O/W method. The results clearly demonstrate that light-responsive PRX/HGNS MS produced using the S/O/W method have the potential to address PD patients' mobility problems in a smart, controllable and remotely triggerable manner.

Keywords: Hollow gold nanospheres; Microspheres; Near-infrared responsive; Parkinson’s disease; Pramipexole.

MeSH terms

  • Biodegradable Plastics / chemistry*
  • Capsules / chemistry
  • Drug Delivery Systems / methods
  • Drug Liberation / drug effects
  • Emulsions / chemistry
  • Humans
  • Infrared Rays
  • Microspheres
  • Nanospheres / chemistry*
  • Parkinson Disease / drug therapy*
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Pramipexole / administration & dosage*
  • Pramipexole / chemistry*
  • Solvents / chemistry

Substances

  • Biodegradable Plastics
  • Capsules
  • Emulsions
  • Solvents
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Pramipexole