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Surfactant-Free Glibenclamide Nanoparticles: Formulation, Characterization and Evaluation of Interactions with Biological Barriers

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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.

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Funding

The authors acknowledge financial support from the Universidad Nacional de Rosario (U.N.R., Rosario, Argentina), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Argentina) and Deutscher Akademischer Austauschdienst (DAAD, Deutschland). ECA thanks to CONICET for a Ph.D. fellowship. OH thanks to the EU Horizon 2020 research and innovation programme under grant Agreement N° 720905–2.

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Authors and Affiliations

  1. IQUIR-CONICET, National Council Research, Institute of Chemistry, Suipacha 531, 2000, Rosario, Argentina

    Eva C. Arrua & Claudio J. Salomon

  2. Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123, Saarbrücken, Germany

    Olga Hartwig, Duy-Khiet Ho, Brigitta Loretz, Xabier Murgia & Claus-Michael Lehr

  3. Department of Pharmacy, Saarland University, 66123, Saarbrücken, Germany

    Olga Hartwig & Claus-Michael Lehr

  4. Pharmacy Department, Faculty of Pharmaceutical and Biochemical Sciences, National University of Rosario, Suipacha 531, 2000, Rosario, Argentina

    Claudio J. Salomon

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  1. Eva C. Arrua
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Arrua, E.C., Hartwig, O., Ho, DK. et al. Surfactant-Free Glibenclamide Nanoparticles: Formulation, Characterization and Evaluation of Interactions with Biological Barriers. Pharm Res 38, 1081–1092 (2021). https://doi.org/10.1007/s11095-021-03056-2

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