目的 制备小檗碱-氧化锌纳米粒（berberine-zinc oxide nanoparticles，Ber-ZnO NPs）考察其理化性质与体外透皮行为，并探索其透皮机制。方法 采用高压均质法制备Ber-ZnO NPs，以平均粒径、多分散指数（polydispersity index，PDI）作为评价指标进行工艺优化。通过透射电子显微镜（transmission electron microscope，TEM）、紫外-可见光谱（ultraviolet-visible spectroscopy，UV-Vis）、傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FTIR）及X射线衍射（X-ray diffraction，XRD）等手段对Ber-ZnO NPs的形貌及理化性质进行表征。利用Franz扩散池考察Ber-ZnO NPs的体外透皮性能并结合扫描电镜探究透皮机制。结果 所制得Ber-ZnO NPs的平均粒径为（219.75±0.89）nm，PDI为0.21±0.02，ζ电位为（15.96±1.63）mV。TEM结果显示，Ber-ZnO NPs呈类圆形纳米团簇结构；UV-Vis及FTIR结果提示，小檗碱可能通过氢键成功负载于ZnO表面。XRD结果显示，Ber-ZnO NPs的结晶度显著降低，表明小檗碱与ZnO之间存在较强的相互作用。在体外透皮实验中，Ber-ZnO NPs在24 h内的累积透过量为（1 431.98±298.31）μg/cm²，是小檗碱溶液的6.6倍，皮肤滞留量为小檗碱溶液的2.6倍。SEM结果显示，Ber-ZnO NPs可明显改变皮肤角质层结构，增强药物的渗透能力。结论 采用高压均质法制备的Ber-ZnO NPs粒径小、分散性好，能够显著提高小檗碱的体外透皮能力，为小檗碱的经皮给药系统的开发提供了新的思路。

Objective To prepare berberine-zinc oxide nanoparticles (Ber-ZnO NPs) using the high-pressure homogenization method, assess their physicochemical characteristics and transdermal behavior in vitro, and elucidate their transdermal mechanism. Methods Ber-ZnO NPs were prepared via high-pressure homogenization, with the average particle size and polydispersity index (PDI) serving as optimization parameters. The morphology and physicochemical properties of Ber-ZnO NPs were analyzed using transmission electron microscopy (TEM), ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Transdermal properties of Ber-ZnO NPs were evaluated using Franz diffusion cells, while scanning electron microscopy was employed to investigate the transdermal mechanism. Results The Ber-ZnO nanoparticles exhibited an average particle size of (219.75 ± 0.89) nm, a polydispersity index (PDI) of 0.21 ± 0.02, and a ζ potential of (15.96 ± 1.63) mV. TEM analysis revealed the quasi-spherical nanocluster-like structure of Ber-ZnO NPs. Spectroscopic analyses, including UV-Vis and FTIR, suggested successful berberine immobilization on the ZnO surface through hydrogen bonding. XRD results indicated a notable reduction in the crystallinity of Ber-ZnO NPs, indicating a robust interaction between berberine and ZnO. In vitro studies demonstrated that the cumulative penetration of Ber-ZnO NPs reached (1 431.98 ± 298.31) μg/cm² within 24 h, representing a 6.6-fold increase compared to berberine solution, with skin retention being 2.6 times higher than that of berberine solution. Scanning electron microscopy (SEM) images illustrated the significant alteration of the stratum corneum structure by Ber-ZnO NPs, leading to enhanced drug penetration. Conclusion Ber-ZnO NPs, synthesized via high-pressure homogenization, exhibit small particle size and excellent dispersibility, significantly enhancing the transdermal delivery of berberine in vitro, thereby offering a novel approach for developing a berberine transdermal delivery system.

R283.6

军队医疗与医药服务能力建设与提升专项计划（2023ZY031）