ACQ-based hybrid nanocrystals enable particokinetics assessment and unravel the in vivo fate of meloxicam nanocrystals

Résumé fourni par la source

The clinical translation of nanocrystal-based nanomedicines is significantly hindered by the lack of suitable methods for particokinetic analysis, as conventional techniques are unable to track intact nanocrystals quantitatively. The hybrid nanocrystal (HNC) technique, which incorporates aggregation-caused quenching (ACQ) probes into the crystal lattice without affecting its intrinsic properties, offers a promising alternative by generating a fluorescence signal that diminishes upon nanocrystal dissolution. This fluorescence change can thus be utilized to quantify nanocrystal concentrations. In this study, meloxicam (MLX) HNCs were fabricated to mimic key characteristics of Anjeso®, including size, crystallinity, dissolution behavior, and pharmacokinetics. The correlation between fluorescence quenching and nanocrystal dissolution was first confirmed in vitro , while a fluorescent calibration curve was established for the quantification of MLX-HNCs. Following intravenous administration in rats, particokinetics were assessed via blood fluorescence. The particokinetic profile deviated from the pharmacokinetic curve (based on plasma MLX concentration) after 2h, indicating gradual nanocrystal dissolution. Only 4.1% of MLX was released within 2h, increasing to 28.8% by 4h. Fluorescence imaging revealed prolonged nanocrystal retention in the mononuclear phagocyte system (MPS) for up to 24h, consistent with slow dissolution. This sustained release profile, likely mediated by protein corona formation, explains the delayed onset and insufficient late-stage analgesia of Anjeso®. The ACQ-based HNC technique thus provides a proof-of-concept methodology for direct particokinetic evaluation, offering crucial insights into nanocrystal fate in vivo and establishing a framework applicable to similar nanocarrier systems.

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