Preparation and evaluation of wet-milled usnic acid nanocrystal suspension for better bioaffinity

Objective: To prepare a new nanosystem of usnic acid (UA) with higher solid content and higher bioavailability.

Methods: Usnic acid nanocrystal suspensions were prepared by the wet milling method, and then the particle size distributions and zeta potential were determined with the Nano ZS90 laser diffraction particle size analyzer. The particles morphology of UA-NCS were observed by scanning electron microscopy method. In addition, solubility and dissolution of UA-NCS in water and phosphate buffer solution were determined in vitro, analyzed by the HPLC method, and then the cellular uptake and pharmacokinetic were carried out on the Caco-2 cells and rats, analyzed by the UPLC-MS/MS method.

Results: Particle size distributions and zeta potential of the UA nanocrystal suspension were 268.7 ± 4.0 nm and –23.1 ± 0.7 mV, respectively. About the dissolution rate of UA, nanosuspension were significantly faster and higher than common suspension in water and phosphate buffer. And in cellular uptake experiments, the ratio of the maximum amount of drug in unit protein of UA nanosuspension to common suspension was 2.8 times. In rats, oral absorption of nanocrystal UA were superior to the ordinary groups, with the 348% of the maximum concentration and 181% of the AUC after the same dosage administration.

Conclusion: The wet-milling technique was suitable for the preparation of UA nanocrystal suspension, and a new nanosystem of UA with higher solid content and higher bioavailability was achieved.