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pH值驱动盐酸小檗碱自组装纳米粒的制备、表征及透皮性能评价

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中草药 | 药剂与工艺 2026,57(19): 7548-7559

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中草药 |药剂与工艺 2026 , 57 (19) : 7548 -7559

pH值驱动盐酸小檗碱自组装纳米粒的制备、表征及透皮性能评价

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王润^1,2, 沈成英³, 宁文洁², 宋芮², 薛凯琳², 杭凌宇², 袁海龙²

作者信息

通讯作者:

杭凌宇

作者简介:

王润: 王润，硕士研究生，研究方向为中药制剂。E-mail:2293871251@qq.com

Preparation, characterization and transdermal performance evaluation of pH-driven self-assembled berberine hydrochloride nanoparticles

WANG Run^1,2, SHEN Chengying³, NING Wenjie², SONG Rui², XUE Kailin², HANG Lingyu², YUAN Hailong²

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doi: 10.7501j.issn.0253-2670.2026.19.006

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摘要

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目的制备盐酸小檗碱自组装纳米粒（berberine hydrochloride self-assembled nanoparticles，BBH-SAN），在无需载体材料的前提下，实现稳定自组装，并系统评价其理化性质及体外透皮性能。方法采用pH驱动法制备BBH-SAN，以平均粒径、多分散指数（polydispersity index，PDI）作为评价指标优化工艺。运用扫描电子显微镜（scanning electron microscopy，SEM）、傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FT-IR）、热重分析（thermogravimetric analysis，TG）及X射线衍射（X-ray diffraction，XRD）分析进行表征；结合分子动力学模拟揭示自组装行为；通过体外透皮实验考察药物透皮性能。结果制备的BBH-SAN在SEM下呈片状结构，平均粒径为（385.67±13.50）nm，PDI为0.06±0.04，ζ电位为（-34.03±1.01）mV，包封率为（87.57±0.05）%。XRD结果显示，BBH-SAN衍射峰重构与结晶度下降，FT-IR特征峰展宽与减弱，提示BBH由规则晶态向低晶态聚集转变。分子动力学模拟揭示，BBH-SAN的形成是由范德华相互作用主导，静电相互作用调控，氢键网络协同稳定的自组装过程。体外透皮实验中，BBH-SAN在24 h内的累积透过量（Qn）为（61.25±1.78）μg/cm²，皮肤滞留量（Qs）、真皮滞留量（Qd）和角质层滞留量（Qsc）均显著高于BBH原料药（P＜0.001）。结论通过加热辅助pH值驱动法，无需载体即可实现BBH的稳定自组装，所得纳米粒粒径均一、分散性好、热稳定优异，并显著改善透皮性能，为生物碱类药物的自组装递送提供了新策略。

关键词

盐酸小檗碱 / 自组装纳米粒 / 体外透皮 / 分子动力学模拟 / 经皮给药 / pH驱动

Abstract

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Objective To prepare berberine hydrochloride self-assembled nanoparticles (BBH-SAN) and realize stable self-assembly of BBH without carrier materials, and to systematically evaluate its physicochemical properties and in vitro transdermal performance. Methods BBH-SAN were prepared using a heat-assisted pH-driven method, with average particle size and polydispersity index (PDI) as evaluation indicators for process optimization. The nanoparticles were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TG), and X-ray diffraction (XRD). Molecular dynamics simulations were employed to elucidate the self-assembly mechanism of BBH-SAN, and in vitro transdermal experiments were conducted to investigate the drug’s transdermal performance. Results The prepared BBH-SAN exhibited lamellar sheet structures under SEM, with an average particle size of (385.67 ± 13.50) nm, a PDI of 0.06 ± 0.04, the ζ potential was determined to be (−34.03 ± 1.01) mV, and an encapsulation efficiency of (87.57 ± 0.05)%. XRD results indicated peak reconstruction and reduced crystallinity, while FT-IR revealed broadening and attenuation of characteristic peaks, suggesting a transition of BBH from a regular crystalline state to a low-crystalline aggregated form. Molecular dynamics simulations revealed that the formation of BBH-SAN is a self-assembly process dominated by van der Waals interactions, regulated by electrostatic interactions, and stabilized synergistically by hydrogen-bond networks. In the in vitro transdermal experiments, the cumulative permeation amount of BBH-SAN within 24 h was (61.25 ± 1.78) μg/cm², and the skin retention (Q_s), dermal retention (Q_d), and stratum corneum retention (Q_sc) of BBH-SAN were all significantly higher than those of BBH (P < 0.001). Conclusion This study achieved the stable self-assembly of berberine hydrochloride without the use of any carrier through a heat-assisted pH-driven method. The resulting nanoparticles exhibit uniform particle size, good dispersibility, excellent thermal stability, and significantly improved transdermal performance, providing a new strategy for the self-assembly delivery of alkaloid drugs.

Key words

berberine hydrochloride / self-assembled nanoparticles / in vitro transdermal / molecular dynamics simulation / transdermal drug delivery / pH-driven

引用本文

王润, 沈成英, 宁文洁, 宋芮, 薛凯琳, 杭凌宇, 袁海龙. pH值驱动盐酸小檗碱自组装纳米粒的制备、表征及透皮性能评价. 中草药, 2026 , 57 (19) : 7548 -7559 . DOI: 10.7501j.issn.0253-2670.2026.19.006

WANG Run, SHEN Chengying, NING Wenjie, SONG Rui, XUE Kailin, HANG Lingyu, YUAN Hailong. Preparation, characterization and transdermal performance evaluation of pH-driven self-assembled berberine hydrochloride nanoparticles[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (19) : 7548 -7559 . DOI: 10.7501j.issn.0253-2670.2026.19.006

基金

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军队医疗与医药服务能力建设与提升专项计划 (2023ZY031); 空军特色医学中心人才培养计划 (2025RCQN02); 空军特色医学中心人才培养计划 (2025RCQN11)

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2026年第57卷第19期

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doi: 10.7501j.issn.0253-2670.2026.19.006

接收时间：2026-04-29
首发时间：2026-10-29

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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