PLGA/DPPC/trimethylchitosan spray-dried microparticles for the nasal delivery of ropinirole hydrochloride: in vitro, ex vivo and cytocompatibility assessment

Mater Sci Eng C Mater Biol Appl. 2016 Feb:59:1053-1062. doi: 10.1016/j.msec.2015.11.028. Epub 2015 Nov 11.

Abstract

In the present study we investigated polymer-lipid microparticles loaded with ropinirole hydrochloride (RH) for nasal delivery. RH microparticles were further evaluated by means of scanning electron microscopy (SEM), ζ-potential measurements, Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and x-ray diffraction (XRD). In vitro release studies were performed in simulated nasal electrolyte solution (SNES) pH5.5 at 35°C. Ex vivo permeation studies were conducted across sheep nasal mucosa. Cytocompatibility was tested in cultured human airway epithelial cells (Calu-3). SEM studies revealed spheroid microparticles in the range of 2.09μm to 2.41μm. The presence of trimethylchitosan (TMC) induced a slight shift towards less negative ζ-potential values. Surface chemistry (XPS) revealed the presence of dipalmitoylphospatidylcholine (DPPC) and poly(lactic-co-glycolic acid) (PLGA) onto microparticles' surface, further corroborating the FT-IR and XRD findings. In vitro release studies showed that the microparticle composition can partly modulate the release of RH. Ex vivo studies demonstrated a 2.35-folded enhancement of RH permeation when RH was co-formulated with TMC of low molecular weight, compared to the control. All formulations tested were found to be non-toxic to cells. The results suggest that polymer-lipid microparticles may be a promising carrier for the nasal delivery of RH.

Keywords: Calu-3 cell line; Ex vivo permeation; Hybrid microparticles; Nasal delivery; Parkinson disease; Spray drying.

MeSH terms

  • 1,2-Dipalmitoylphosphatidylcholine / chemistry*
  • 1,2-Dipalmitoylphosphatidylcholine / toxicity
  • Administration, Intranasal
  • Animals
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / chemistry
  • Antiparkinson Agents / pharmacokinetics
  • Cell Line
  • Cell Survival / drug effects
  • Chitosan / chemistry*
  • Chitosan / toxicity
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • Humans
  • Indoles / administration & dosage*
  • Indoles / chemistry
  • Indoles / pharmacokinetics
  • Lactic Acid / chemistry*
  • Nasal Mucosa / metabolism
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Sheep

Substances

  • Antiparkinson Agents
  • Drug Carriers
  • Indoles
  • N-trimethyl chitosan chloride
  • ropinirole
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • 1,2-Dipalmitoylphosphatidylcholine
  • Lactic Acid
  • Chitosan