Development of meloxicam-human serum albumin nanoparticles for nose-to-brain delivery via application of a quality by design approach

Gábor Katona, György Tibor Balogh, Gergő Dargó, Róbert Gáspár, Árpád Márki, Eszter Ducza, Anita Sztojkov-Ivanov, Ferenc Tömösi, Gábor Kecskeméti, Tamás Janáky, Tamás Kiss, Rita Ambrus, Edina Pallagi, Piroska Szabó-Révész, Ildikó Csóka

Research output: Contribution to journalArticle

Abstract

The aim of this study was to optimize the formulation of meloxicam (MEL)-containing human serum albumin (HSA) nanoparticles for nose-to-brain via a quality by design (QbD) approach. Liquid and dried formulations of nanoparticles containing Tween 80 and without the surfactant were investigated. Various properties, such as the Z-average, zeta potential, encapsulation efficacy (EE), conjugation of MEL and HSA, physical stability, in vitro dissolution, in vitro permeability, and in vivo plasma and brain distribution of MEL were characterized. From a stability point of view, a solid product (Mel-HSA-Tween) is recommended for further development since it met the desired critical parameters (176 ± 0.3 nm Z-average, 0.205 ± 0.01 PdI, −14.1 ± 0.7 mV zeta potential) after 6 months of storage. In vitro examination showed a significantly increased drug dissolution and permeability of MEL-containing nanoparticles, especially in the case of applying Tween 80. The in vivo studies confirmed both the trans-epithelial and axonal transport of nanoparticles, and a significantly higher cerebral concentration of MEL was detected with nose-to-brain delivery, in comparison with intravenous or per os administration. These results indicate intranasal the administration of optimized MEL-containing HSA formulations as a potentially applicable “value-added” product for the treatment of neuroinflammation.

Original languageEnglish
Article number97
JournalPharmaceutics
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2020

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Keywords

  • HSA nanoparticles
  • In vivo animal studies
  • Meloxicam
  • Nose-to-brain delivery
  • PAMPA
  • Physical stability
  • Quality by design
  • Rapid equilibrium dialysis

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Katona, G., Balogh, G. T., Dargó, G., Gáspár, R., Márki, Á., Ducza, E., Sztojkov-Ivanov, A., Tömösi, F., Kecskeméti, G., Janáky, T., Kiss, T., Ambrus, R., Pallagi, E., Szabó-Révész, P., & Csóka, I. (2020). Development of meloxicam-human serum albumin nanoparticles for nose-to-brain delivery via application of a quality by design approach. Pharmaceutics, 12(2), [97]. https://doi.org/10.3390/pharmaceutics12020097