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

• Published in: Journal of microencapsulation Vol. 40; no. 2; pp. 67 - 81
• Main Authors: Reis Nascimento, Ruan, Pauline Gaitan Tabares, Julie, Marques dos Anjos, Paulo Neilson, Santos, Luana Novaes, de Oliveira Silva, Denise, Silva Ribeiro Santos, Rodrigo Luis
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 17-02-2023
• Subjects: anti-inflammatory drugs; biodegradable polymers; Drug Carriers - chemistry; drug delivery systems; Metallodrug; microwave-induced plasma; Microwaves; Nanoparticles - chemistry; Naproxen; Particle Size; Polyesters - chemistry; Polymers - chemistry; Ruthenium; Spectrum Analysis; drug delivery systems; microwave-induced plasma; anti-inflammatory drugs; Metallodrug; biodegradable polymers
• ISSN: 0265-2048; 1464-5246
• DOI: 10.1080/02652048.2023.2172469

The objectives of this work are to develop nanocarrier systems for the Ru(II)-p-cymene naproxen antitumor metallodrug, [Ru(η
6
-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.