Work

A direct, real-time, size-resolved analytical strategy to follow drug loading and release from biocompatible gold nanoparticles

Year: 2025

Type: article

Abstract: BACKGROUND: Analytical methods for the characterization of nanoparticle-based drug delivery systems often rely on the quantification of unbound drug to provide information on drug loading and delivery, but fail to account for system complexity, address the state of the releasing system, or simulate the physiological environment. There is a clear need for new analytical methods capable of following the entire process of drug loading, stability and release under physiological conditions, based on multi-parametric analytical platforms. Asymmetric flow field-flow fractionation (AF4) can be used to size sort and isolate nanoparticles for further analysis or characterization by online, uncorrelated techniques. RESULTS: We propose AF4 coupled with online multiple detectors to investigate the model drug delivery system consisting of albumin (BSA)-coated gold nanoparticles (AuNPs) loaded with curcumin (CUR). A maximum loading efficiency of 88.9 % is achieved by optimizing various experimental parameters. The absorbance ratio of nanocarriers at 401 nm and 530 nm was successfully proposed as an index for evaluating drug loading (full load was 0.77 ± 0.01) and release from the carrier surface. At 37 °C, Au-BSA-CUR exhibits rapid drug release, achieving 34.8 % total release. This process is accompanied by swift degradation and efficient diffusion of the drug into the surrounding reservoir (∼30 %). The appearance of new absorbance peaks in fractograms (curcumin aggregation) at lower temperatures (20 or 30 °C) indicates the special properties of hydrophobic drugs, which are monitored by the AF4 platform for the first time. SIGNIFICANCE: The tailored strategy employed in our investigation provided detailed, real-time, in situ analysis, making it a powerful tool for designing and optimizing drug delivery systems, providing insight into both loading and release mechanisms, assessing nanoparticle stability, and tolerating saline media. These results suggest that AF4-DAD-MALS is a more reliable and insightful technique for studying the stability, loading efficiency, and release dynamics of nanoparticle-based drug delivery systems.

Source: Analytica Chimica Acta

DOI: 10.1016/j.aca.2025.344246