Supersaturated Drug Delivery System of Oxyberberine Based on Cyclodextrin Nanoaggregates: Preparation, Characterization, and in vivo Application

• Published in: International journal of nanomedicine 2024-01, Vol.19, p.5297-5316
• Main Authors: Huang, Ziwei, Zhang, Shanli, Qin, Zehui, Ai, Gaoxiang, Li, Minhua, Gong, Shiting, Liu, Yuhong, Zeng, Huifang, Chen, Jiannan, Su, Ziren, Lai, Zhengquan
• Format: Article
• Language: English
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin - chemistry; 2-Hydroxypropyl-beta-cyclodextrin - pharmacokinetics; Animals; Berberine - administration & dosage; Berberine - chemistry; Berberine - pharmacokinetics; Berberine - pharmacology; Biological Availability; cyclodextrin; Drug Delivery Systems - methods; Drug Liberation; hyperuricemia; Hyperuricemia - blood; Hyperuricemia - drug therapy; Male; Nanoparticles - chemistry; Original Research; oxyberberine; Particle Size; pharmacokinetics; Rats; Rats, Sprague-Dawley; Solubility; supersaturated drug delivery systems; Uric Acid - blood; Uric Acid - chemistry
• ISSN: 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S464994

Oxyberberine (OBB), one of the main metabolites of berberine derived from intestinal and erythrocyte metabolism, exhibits appreciable anti-hyperuricemic activity. However, the low water solubility and poor plasma concentration-effect relationship of OBB hamper its development and utilization. Therefore, an OBB-hydroxypropyl-β-cyclodextrin (HP-β-CD) supersaturated drug delivery system (SDDS) was prepared and characterized in this work. OBB-HP-β-CD SDDS was prepared using the ultrasonic-solvent evaporation method and characterized. Additionally, the in vitro and in vivo release experiments were conducted to assess the release kinetics of OBB-HP-β-CD SDDS. Subsequently, the therapeutic efficacy of OBB-HP-β-CD SDDS on hyperuricemia (HUA) was investigated by means of histopathological examination and evaluation of relevant biomarkers. The results of FT-IR, DSC, PXRD, NMR and molecular modeling showed that the crystallized form of OBB was transformed into an amorphous OBB-HP-β-CD complex. Dynamic light scattering indicated that this system was relatively stable and maintained by formation of nanoaggregates with an average diameter of 23 nm. The dissolution rate of OBB-HP-β-CD SDDS was about 5 times higher than that of OBB raw material. Furthermore, the of OBB-HP-β-CD SDDS (10.882 μg/mL*h) was significantly higher than that of the raw OBB counterpart (0.701 μg/mL*h). The oral relative bioavailability of OBB-HP-β-CD SDDS was also enhanced by 16 times compared to that of the raw material. Finally, in vivo pharmacodynamic assay showed the anti-hyperuricemic potency of OBB-HP-β-CD SDDS was approximately 5-10 times higher than that of OBB raw material. Based on our findings above, OBB-HP-β-CD SDDS proved to be an excellent drug delivery system for increasing the solubility, dissolution, bioavailability, and anti-hyperuricemic potency of OBB.