Xue Fei, Yang Lan, Ma Shuai, Chang Jin Hua, Liu Pei, Liu Xi Gang, Wang Ru Xing
Institute of Chinese Materia Medica, Chengde Medical University, Hebei Province Key Laboratory of Research and Development for Chinese Materia Medica, Chengde Hebei Province, 067000, P.R. China.
Curr Drug Deliv. 2025;22(5):648-657. doi: 10.2174/0115672018341709241121092617.
INTRODUCTION/BACKGROUND: Tetrandrine (TET) has multiple pharmacological activities, but its water solubility is poor, which is the main reason for its low bioavailability.
The purpose of this study was to prepare TET nanocrystals (TET-NCs) using a grinding method to enhance the dissolution rate and ultimately improve the bioavailability of TET.
TET-NCs were synthesized via media milling, employing Poloxam 407 (P407) as surface stabilizer and mannitol as a cryoprotectant during freeze-drying. The crystal structure, particle diameter, and zeta potential were characterized using differential scanning calorimetry (DSC), Fouriertransform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The in vitro release behavior and pharmacokinetics of TET-NCs were assessed. The cytotoxicity of TET and TET-NCS on RAW264.7 cells was determined by the CCK-8 method.
The particle size of TET-NCs was 360.0±7.03 nm, PDI was 0.26±0.03, and zeta potential was 6.64±0.22 mV. The cumulative dissolution within 60 minutes was 96.40±2.31%. The pharmacokinetic study showed that AUC0-72 h and Cmax of TET-NCs were significantly enhanced by 3.07 and 2.57 times, respectively, compared with TET (p<0.01). TET-NCs significantly increased the cell inhibition on RAW264.7 cells compared to the TET (P<0.01).
The preparation of TET-NCs enhanced dissolution rate and bioavailability significantly, and it also improved the inhibition effect of RAW264.7 cells.
引言/背景：粉防己碱（TET）具有多种药理活性，但其水溶性较差，这是其生物利用度低的主要原因。
本研究旨在采用研磨法制备TET纳米晶体（TET-NCs），以提高其溶解速率并最终改善TET的生物利用度。
通过介质研磨合成TET-NCs，在冷冻干燥过程中使用泊洛沙姆407（P407）作为表面稳定剂，甘露醇作为冷冻保护剂。使用差示扫描量热法（DSC）、傅里叶变换红外光谱（FT-IR）、扫描电子显微镜（SEM）和X射线衍射（XRD）对晶体结构、粒径和zeta电位进行表征。评估了TET-NCs的体外释放行为和药代动力学。采用CCK-8法测定TET和TET-NCS对RAW264.7细胞的细胞毒性。
TET-NCs的粒径为360.0±7.03nm，PDI为0.26±0.03，zeta电位为6.64±0.22mV。60分钟内的累积溶出率为96.40±2.31%。药代动力学研究表明，与TET相比，TET-NCs的AUC0-72h和Cmax分别显著提高了3.07倍和2.57倍（p<0.01）。与TET相比，TET-NCs对RAW264.7细胞的抑制作用显著增强（P<0.01）。
TET-NCs的制备显著提高了溶解速率和生物利用度，同时也增强了对RAW264.7细胞的抑制作用。
