ORMOSIL nanoparticles as drug delivery carriers for oxaliplatin: formulation development and characterization

This study aimed to investigate the influence of formulation and process variables on the physicochemical properties and drug release behavior of oxaliplatin (OXP)-loaded ORMOSIL (Organically Modified Silicate) nanoparticles. ORMOSIL nanoparticles were synthesized using sol-gel methods, employing co-condensation (addition of TEOS and APTES at the beginning of the hydrolysis) and post-modification (adding APTES in hydrolyzed silica sol) approaches. Key parameters, pH of the hydrolysis process, water/alkoxide ratio, and preparation method, were systematically explored. The formulations demonstrated average diameter in the range of 111–296 nm, with a unimodal size distribution (PDI). Drug content (DC) ranged 2.42–8.39 µg OXP/mg nanoparticles, and the dissolution pattern was characterized by an initial burst release followed by a slower drug release phase. The post-modification method yielded higher DC, attributed to matrix structure differences which were also validated by distinctive features in FTIR and Raman spectra. XRD and DSC studies demonstrated that OXP was completely entrapped in the silica matrix in its amorphous form, regardless of the preparation method. Further studies were focused on investigating the post-modification method, as it presented more promising formulation properties in regards to the DC. A study design guided by central composite response surface methodology revealed relationships between variables (pH, water, oxaliplatin quantity) and responses (particle size, PDI, DC, zeta potential). Particle sizes ranged from 274 to 2285 nm, PDI from 0.129 to 0.958, DC from 3.81 to 37.08 µg OXP/mg NPs, with positive zeta potential (0.83–28.3 mV). The PLS exploratory multivariate statistical analysis highlighted an increase in particle size and PDI under acidic pH and a positive correlation between OXP quantity and DC and inverse relationship between water quantity and nanoparticle zeta potential.