Eva C Arrua1, Olga Hartwig2,3, Duy-Khiet Ho2, Brigitta Loretz2, Xabier Murgia4, Claudio J Salomon5,6, Claus-Michael Lehr7,8. 1. IQUIR-CONICET, National Council Research, Institute of Chemistry, Suipacha 531, 2000, Rosario, Argentina. 2. Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123, Saarbrücken, Germany. 3. Department of Pharmacy, Saarland University, 66123, Saarbrücken, Germany. 4. Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123, Saarbrücken, Germany. xmurgia@kusudama.eu. 5. IQUIR-CONICET, National Council Research, Institute of Chemistry, Suipacha 531, 2000, Rosario, Argentina. csalomon@fbioyf.unr.edu.ar. 6. Pharmacy Department, Faculty of Pharmaceutical and Biochemical Sciences, National University of Rosario, Suipacha 531, 2000, Rosario, Argentina. csalomon@fbioyf.unr.edu.ar. 7. Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123, Saarbrücken, Germany. Claus-Michael.Lehr@helmholtz-hips.de. 8. Department of Pharmacy, Saarland University, 66123, Saarbrücken, Germany. Claus-Michael.Lehr@helmholtz-hips.de.
Abstract
PURPOSE: The aim of this work was to formulate and characterize surfactant-free glibenclamide nanoparticles using Eudragit RLPO and polyethylene glycol as sole stabilizer. METHODS: Glibenclamide nanoparticles were obtained by nanoprecipitation and evaluated in terms of drug content, encapsulation efficiency, apparent saturation solubility, drug release profile, solid state and storage stability. The influence of different stirring speed on the particle size, size distribution and zeta potential of the nanoparticles was investigated. The nanoparticle biocompatibility and permeability were analyzed in vitro on Caco-2 cell line (clone HTB-37) and its interaction with mucin was also investigated. RESULTS: It was found that increasing the molecular weight of polyethylene glycol from 400 to 6000 decreased drug encapsulation, whereas the aqueous solubility and dissolution rate of the drug increased. Particle size of the nanoformulations, with and without polyethylene glycol, were between 140 and 460 nm. Stability studies confirmed that glibenclamide nanoparticles were stable, in terms of particle size, after 120 days at 4°C. In vitro studies indicated minimal interactions of glibenclamide nanoparticles and mucin glycoproteins suggesting favorable properties to address the intestinal mucus barrier. Cell viability studies confirmed the safety profile of these nanoparticles and showed an increased permeation through epithelial cells. CONCLUSION: Taking into consideration these findings, polyethylene glycol is a useful polymer for stabilizing these surfactant-free glibenclamide nanoparticles and represent a promising alternative to improve the treatment of non-insulin dependent diabetes.
PURPOSE: The aim of this work was to formulate and characterize surfactant-free glibenclamide nanoparticles using Eudragit RLPO and polyethylene glycol as sole stabilizer. METHODS: Glibenclamide nanoparticles were obtained by nanoprecipitation and evaluated in terms of drug content, encapsulation efficiency, apparent saturation solubility, drug release profile, solid state and storage stability. The influence of different stirring speed on the particle size, size distribution and zeta potential of the nanoparticles was investigated. The nanoparticle biocompatibility and permeability were analyzed in vitro on Caco-2 cell line (clone HTB-37) and its interaction with mucin was also investigated. RESULTS: It was found that increasing the molecular weight of polyethylene glycol from 400 to 6000 decreased drug encapsulation, whereas the aqueous solubility and dissolution rate of the drug increased. Particle size of the nanoformulations, with and without polyethylene glycol, were between 140 and 460 nm. Stability studies confirmed that glibenclamide nanoparticles were stable, in terms of particle size, after 120 days at 4°C. In vitro studies indicated minimal interactions of glibenclamide nanoparticles and mucin glycoproteins suggesting favorable properties to address the intestinal mucus barrier. Cell viability studies confirmed the safety profile of these nanoparticles and showed an increased permeation through epithelial cells. CONCLUSION: Taking into consideration these findings, polyethylene glycol is a useful polymer for stabilizing these surfactant-free glibenclamide nanoparticles and represent a promising alternative to improve the treatment of non-insulin dependent diabetes.
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