盐酸小檗碱透过羧甲基壳聚糖-海藻酸钠聚电解质水凝胶的规律研究

Study on the Rule of Berberine Hydrochloride Through Carboxymethyl Chitosan-sodium Alginate Polyelectrolyte Hydrogel

关键词:  盐酸小檗碱  羧甲基壳聚糖  海藻酸钠  聚电解质  水凝胶

Key words:  berberine hydrochloride  carboxymethyl chitosan  sodium alginate  polyelectrolyte  hydrogel

摘要:

目的 探究伤科黄水中黄连和黄柏的主要有效成分盐酸小檗碱(berberine hydrochloride，BBH)在羧甲基壳聚糖(carboxymethyl chitosan，CMCS)-海藻酸钠(sodium alginate，SA)体系中的传递与扩散规律。方法 CMCS和SA按照一定比例搅拌，加入D-葡萄糖酸内酯(D-gluconolactone，GDL)后形成聚电解质水凝胶。采用流变仪研究CMCS-SA的水凝胶的流变学性能，包括弹性模量G'和黏性模量G''。设计针对CMCS-SA水凝胶的BBH扩散模型并通过UV观察BBH透过CMCS-SA聚电解质水凝胶的相关规律。结果 测定CMCS与SA配比为3∶1，2∶1，1∶1，1∶2，1∶3时的水凝胶弹性模量G'，当CMCS∶SA=1∶1时，G'最高，此时水凝胶交联强度最高。通过BBH传递模型测定其累积传递量，经Peppas方程拟合BBH在CMCS-SA水凝胶中的扩散为骨架溶蚀作用，表明随着CMCS的氨基减少或SA的羧基增加，BBH解离，传递效率增加。CMCS-SA水凝胶的弹性模量G'随着GDL含量增加而增加，是因为pH的降低导致CMCS和SA分子间的结合力逐渐增加，水凝胶交联度增强。固定CMCS与SA比例1∶1，GDL含量0.15 g·mL^-1，CMCS-SA水凝胶成型性良好。此外BBH在不同浓度GDL的水凝胶中传递时，随着GDL含量增加，传递效率上升。BBH在不同厚度水凝胶中传递时，随着厚度减小，CMCS-SA水凝胶的传递效率增加。结论 CMCS-SA水凝胶体系作为潜在的BBH等中药提取物的药物载体有望作为经皮给药的凝胶载体。

Abstract:

OBJECTIVE To investigate the transfer and diffusion of berberine hydrochloride(BBH), the main active component of Coptis and Phellodenticum in the system of carboxymethyl chitosan(CMCS)-sodium alginate(SA). METHODS CMCS and SA were stirred in a certain proportion, and D-gluconolactone(GDL) was added to form polyelectrolyte hydrogel. Rheometer was used to study the rheological properties of CMCS-SA hydrogel, including the elastic modulus G' and the viscous modulus G''. A BBH diffusion model for CMCS-SA hydrogel was designed, and the relevant rules of BBH permeation through CMCS-SA polyelectrolyte hydrogel were observed by UV-VIS. RESULTS The elastic modulus G' of the hydrogel was measured when the ratio of CMCS to SA was 3∶1, 2∶1, 1∶1, 1∶2, and 1∶3. When the ratio of CMCS to SA was 1∶1, G' was the highest, and the crosslinking strength of the hydrogel was the highest. The cumulative amount of BBH transfer was measured by the BBH transfer model, and the diffusion of BBH in CMCS-SA hydrogel was fitted as the skeleton dissolution by Peppas equation, indicating that BBH dissociation and the transfer efficiency increased as the amino group of CMCS decreased or the carboxyl group of SA increased. The elastic modulus G' of CMCS-SA hydrogel increased with the increase of GDL content. The reason was that the binding force between CMCS and SA molecules gradually increased with the decrease of pH, and the crosslinking degree of the hydrogel was enhanced. When ratio of fixed CMCS to SA was 1∶1 and the GDL content was 0.15 g·mL^-1, the formability of CMCS-SA hydrogel was good. In addition, when BBH was transferred in hydrogel with different concentrations of GDL, the transfer efficiency increased with the increase of GDL content. When BBH was delivered in different thickness hydrogel, the delivery efficiency of CMCS-SA hydrogel increased with the decrease of thickness. CONCLUSION The CMCS-SA hydrogel system, as a potential drug carrier for traditional Chinese medicine extracts such as BBH, is expected to serve as a gel carrier for transdermal drug delivery.