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.