Poly(lactic acid)/β-cyclodextrin based nanoparticles bearing ruthenium(II)-arene naproxen complex: preparation and characterisation. Analytical validation for metal determination by microwave-induced plasma optical emission spectrometry

Abstract

The objectives of this work are to develop nanocarrier systems for the Ru(II)-p-cymene naproxen antitumor metallodrug, [Ru(η⁶-p-cymene)(npx)Cl] or Rupcy, based on polymeric nanoparticles (NPs) composed by the biodegradable poly(lactic acid) (PLA) and the hydrophilic polymerised β-cyclodextrin (PolyCD); to validate an analytical method for determination of Ru incorporated into the metallodrug loaded-NPs. The PolyCD was prepared by single step condensation and polymerisation reaction and incorporated as a polymer blend during the fabrication of PLA/PolyCD blends NPs and also as a core/shell structure built by adsorption of the PolyCD onto the surface of PLA NPs to give PLA(core)/PolyCD(shell) NPs. Three different loaded-systems incorporating the metallodrug (Rupcy-PLA NPs (1), Rupcy-PLA/PolyCD blends (2), and Rupcy-PLA(core)/PolyCD(shell) NPs (3)) were prepared by nanoprecipitation. The characterisation was performed by Proton Nuclear Magnetic Resonance, Matrix Assisted Laser Desorption/Ionization Time-of-Flight, Fourier-Transform Infra-red and UV-VIS Electronic Absorption Spectroscopies, Thermogravimetric Analysis, Differential Scanning Calorimetry, Dynamic Light Scattering, and Electrophoretic Light Scattering. Ru was determined by Microwave Induced Plasma Optical Emission Spectrometry (MIP-OES) with validation of the method. The metallodrug entrapment efficiency was around 90% (w/w) and drug loading was at 3–4% (w/w). The characterised metallodrug-loaded systems exhibited monomodal size distributions and appropriate hydrodynamic diameters [218.3 ± 13.5 (1), 205.4 ± 14.4 (2), 231.5 ± 22.0 (3) nm] and zeta potential values [−31.5 ± 2.2 (1), −26.1 ± 4.5 (2), −28.8 ± 6.1 (3) mV]. The validation of the MIP-OES method by evaluating selectivity, linearity, precision, accuracy, and limits of detection and quantification succeeded. The NPs parameters are compatible with colloidally stable systems. The MIP-OES method showed to be simple, reliable, and feasible to quantify indirectly the amount of the metallodrug-loaded into the PLA NPs.

Keywords:

• Metallodrug
• anti-inflammatory drugs
• biodegradable polymers
• drug delivery systems
• microwave-induced plasma

Acknowledgements

The authors thank Prof. Dr. Luiz Carlos Salay (UESC) for providing laboratory facilities to perform the experiments, Julia C. Romero (UESC) for assistance with MIP-OES experiments, and Sandra Cristel Quispe for assistance with laboratory experiments at the IQ-USP.

Disclosure statement

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

Data availability statement

The data that support the findings of this study are available from the corresponding author, R.L.S.R. Santos, upon reasonable request.

Additional information

Funding

R. R. Nascimento and J. P. G. Tabares acknowledge the CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for their master’s degree and doctorate fellowships, respectively. D. O. Silva acknowledges the financial support from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) for research grants (2014/23047-5 and 2018/00297-4) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) for the productivity fellowship (305914/2015-4 and 303103/2018-3).