Formulation and In-Vitro Characterization of Chitosan-Nanoparticles Loaded with the Iron Chelator Deferoxamine Mesylate (DFO)

Pharmaceutics

Dimitra A. Lambropoulou¹  Margaritis Kostoglou²  Maria Lazaridou³  Maria Nerantzaki³  Evi Christodoulou³  Dimitrios N. Bikiaris³  Angeliki Katsarou⁴  Kostas Pantopoulos⁴ 

[1] Laboratory of Environmental Pollution Control, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki, Greece;Laboratory of General and Inorganic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki, Greece;Laboratory of Polymer Chemistry and Technology, Chemistry Department, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;Lady Davis Institute for Medical Research and Department of Medicine, McGill University, Montreal, QC H3T 1E2, Canada;

关键词: chitosan;    nanoparticles;    ionic gelation;    tripolyphosphate;    deferoxamine mesylate;    iron chelator;    nanoencapsulation;    drug release;   

DOI  :  10.3390/pharmaceutics12030238

来源: DOAJ

【 摘 要 】

The objective of this study was to develop chitosan (CS) nanoparticles (NPs) loaded with deferoxamine mesylate (DFO) for slow release of this iron-chelating drug. Drug nanoencapsulation was performed via ionic gelation of chitosan using sodium tripolyphosphate (TPP) as cross-linker. Nanoparticles with a size ranging between 150 and 400 nm were prepared for neat CS/TPP with a 2/1 molar ratio while their yield was directly dependent on the applied stirring rate during the preparation process. DFO at different content (20, 45 and 75 wt %) was encapsulated into these nanoparticles. We found that drug loading correlates with increasing DFO content while the entrapment efficiency has an opposite behavior due to the high solubility of DFO. Hydrogen-bonding between amino and hydroxyl groups of DFO with reactive groups of CS were detected using FT-IR spectroscopy while X-ray diffraction revealed that DFO was entrapped in amorphous form in the CS nanoparticles. DFO release is directly dependent on the content of loaded drug, while model analysis revealed that the release mechanism of DFO for the CS/TPP nanoparticles is by diffusion. Treatment of murine RAW 264.7 macrophages with nanoencapsulated DFO promoted an increased expression of transferrin receptor 1 (TfR1) mRNA, a typical homeostatic response to iron deficiency. These data provide preliminary evidence for release of pharmacologically active DFO from the chitosan nanoparticles.

【 授权许可】

Unknown