Diruthenium(II-III)-ibuprofen-loaded chitosan-based microparticles and nanoparticles systems: encapsulation, characterisation, anticancer activity of the nanoformulations against U87MG human glioma cells

Abstract

The aim of this work was to investigate novel formulations containing diruthenium(II-III)-ibuprofen (RuIbp) metallodrug encapsulated into the chitosan (CT) biopolymer. Microparticles (RuIbp/CT MPs, ∼ 1 µm) were prepared by spray-drying, and RuIbp/CT-crosslinked nanoparticles (NPs) by ionic gelation (RuIbp/CT-TPP, TPP = tripolyphosphate (1), RuIbp/CT-TPP-PEG, PEG = poly(ethyleneglycol (2)) or pre-gel/polyelectrolyte complex method (RuIbp/CT-ALG, ALG = alginate (3)). Ru analysis was conducted by energy dispersive x-ray fluorescence or inductively coupled plasma atomic emission spectroscopy, and physicochemical characterisation by powder x-ray diffraction, electronic absorption and FTIR spectroscopies, electrospray ionisation mass spectrometry, thermal analysis, scanning electron, transition electron and atomic force microscopies, and dynamic light scattering. The RuIbp-loaded nanosystems exhibited encapsulation efficiency ∼ 20–37%, drug loading∼ 10-20% (w/w), hydrodynamic diameter (nm): 103.2 ± 7.9 (1), 91.7 ± 12.6 (2), 270.2 ± 58.4 (3), zeta potential (mV): +(47.7 ± 2.8) (1), +(49.2 ± 3.6) (2), -(28.2 ± 2.0) (3). Nanoformulation (1) showed the highest cytotoxicity with increased efficacy in relation to the RuIbp free metallodrug against U87MG human glioma cells.

Keywords:

• Diruthenium(II,III) compounds
• ibuprofen
• anticancer metallodrugs
• chitosan
• microparticles
• nanoparticles

Acknowledgements

The authors thank Prof. H. E. Toma, Prof. K. Araki, Prof. D. Petri, Prof. F. Rodrigues, Prof. R. Torresi, Prof. Liane Rossi, Dr. M. Nakamura (AFM images), Dr. A. T. S. Junior (EDXRF) for technical support, Dr. R. N. F. Sanches for experimental help, and MSc A. Duarte (TEM experiments, Analytical Centre), at the Institute of Chemistry, University of São Paulo.

Disclosure statement

No potential conflict of interest is reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, D. de Oliveira Silva, upon reasonable request.

Additional information

Funding

The authors acknowledge financial support from: Fundação de Amparo a Pesquisa do Estado de São Paulo [FAPESP], Research grants to D. de Oliveira Silva (2014/23047‑5; 2018/00297–4), Doctorate fellowship to S. R. Alves (2014/23481–7); Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq], Productivity fellowship to D. de Oliveira Silva (305914/2015–4; 303103/2018–3), Master fellowship to B. Fornaciari (170737/2017–9); Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior [CAPES], Doctorate fellowship to Hanif-Ur-Rehman (33002010191P0).