Page 152 - 《精细化工》2020年 第10期

·2082· 精细化工 FINE CHEMICALS 第 37 卷

采用修改的溶剂注入法，并在壳聚糖水相中添加质
量浓度为 20 g/L 的水溶性维生素 E 时制得的纳米粒
具有最大包封率（51.13%）。此时，纳米粒的平均粒
径为 142.23 nm，电位为 24.57 mV，外形类似球形。
自组装纳米粒可显著提高荷叶碱的贮藏稳定性，为
将荷叶碱开发成天然防腐剂提供了参考。胃环境是
荷叶碱在人体中被破坏的主要场所，经胃消化后荷叶
碱保留率仅为 27.30%，经肠消化后保留率仅为
20.29%，自组装纳米粒可显著提高荷叶碱的消化稳
定性，使得荷叶碱经肠消化后保留率达到 82.98%。
图 7 荷叶碱和荷叶碱自组装纳米粒的体外释放曲线
Fig. 7 In vitro release curves of nuciferine and nuciferine 在体外模拟释放实验中荷叶碱自组装纳米粒表现出
from nuciferin-encapsulated self-assembled nanoparticles 一定的缓释性，表明自组装纳米粒具有克服荷叶生
物碱应用障碍的潜力，为荷叶生物碱的进一步利用
表 3 荷叶碱和荷叶碱自组装纳米粒的体外释放模型拟
合结果 提供了理论参考。
Table 3 In vitro release kinetics model fitting results of 参考文献：
nuciferine from nuciferine and nuciferin-encapsulated
self-assembled nanoparticles [1] WANG Y Y (王颖滢). Study on isolation, identification, antimicrobial
activity of alkaloids from lotus leaf[D]. Hangzhou: Zhejiang University
荷叶碱自组装纳
模型 参数 荷叶碱 (浙江大学)，2012
米粒
[2] WANG Y X (王玉霞), LIU B (刘斌), SHI R B (石任兵), et al.
2
Korsmeyer-Peppas R 0.8983 0.9184 Determination of nuciferine in Beagle dog plasma by RP-HPLC and
k 1 31.9027 56.1684 research on its pharmacokinetics[J]. Chinese Journal of Pharmaceutical
Analysis (药物分析杂志), 2008, 28(9): 1418-1421.
n 0.3300 0.1757
[3] WANG F G, CAN J, HOU X Q, et al. Pharmacokinetics, tissue
2
Higuchi R 0.8244 0.6123 distribution, bioavailability, and excretion of nuciferine, an alkaloid
k 2 15.8474 12.5176 from lotus, in rats by LC/MS/MS[J]. Drug Development and Industrial
Pharmacy, 2018, 44(9): 1557-1562.
c 13.1042 37.1075
[4] GERELLI Y, BARI M, DERIU A, et al. Structure and organization of
2
一级模型 R 0.9884 0.9346 phospholipid/polysaccharide nanoparticles[J]. Journal of Physics-
k 3 –0.1648 –0.4409 Condensed Matter, 2008, 20(10): 104211-104218.
[5] DUTTAGUPTA D, JADHAV V, KADAM V. Chitosan: A propitious
c 1 4.5637 4.4998
biopolymer for drug delivery[J]. Current Drug Delivery, 2015, 12(4):
2
零级模型 R 0.5884 0.3717 369-381.
k 3 1.8449 1.3142 [6] GAO L, ZHANG D R, CHEN M H, et al. Studies on pharmacokinetics
and tissue distribution of oridonin nanosuspensions[J]. International
c 2 34.3530 55.4010
Journal of Pharmaceutics, 2008, 355(1/2): 321-327.
[7] REPKA M A, MCGINITY J W. Bioadhesives properties of
与未包埋的荷叶碱相比，荷叶碱自组装纳米粒 hydroxypropylcellulose topical films produced by hot-melt extrusion[J].
的缓释性虽有提升，但幅度并不大。分析原因可能 Journal of Controlled Release, 2001, 70(3): 341-351.
[8] SONVICO F, CAGNANI A, ROSSI A, et al. Formation of
是自组装纳米粒的包封率最大只有 51.13%所致，导 self-organized nanoparticles by lecithin/chitosan ionic interaction[J].
致未被包封的荷叶碱快速扩散到释放介质中，而被 International Journal of Pharmaceutics, 2006, 324(1): 67-73.
[9] LIU L Y, ZHOU C P, XIA X J, et al. Self-assembled lecithin/chitosan
包封的荷叶碱缓慢释放，所以自组装纳米粒的整体
nanoparticles for oral insulin delivery: Preparation and functional
释放速率低于未包封的荷叶碱实验组。在拟合 evaluation[J]. International Journal of Nanomedicine, 2016, 11:
761-769.
Korsmeyer-Peppas 模型中，n 值小于 0.45，即表示荷 [10] SENYIGIT T, SONVICO F, BARBIERI S, et al. Lecithin/chitosan
叶碱在释放介质中以 Fickian 扩散为主 [18] 。这可能是 nanoparticles of clobetaso-17-propionate capable of accumulation in
因为，荷叶碱为亲脂性正电荷药物，而磷脂-壳聚糖 pig skin[J]. Journal of Controlled Release, 2010, 142(3): 368-373.
[11] TAN Q, LIU W D, GUO C Y, et al. Preparation and evaluation of
自组装纳米粒表面电位也为正，同电相斥，导致荷 quercetin-loaded lecithin-chitosan nanoparticles for topical delivery[J].
叶碱并未被吸附在纳米粒表面，所以荷叶碱在释放 International Journal of Nanomedicine, 2011, 6: 1621-1630.
[12] RUTTALA H, RAMASAMY T. Multiple polysaccharide-drug
介质的释放与纳米载体是否消融无关。
complex-loaded liposomes: A unique strategy in drug loading and
cancer targeting[J]. Carbohydrate Polymers, 2017, 173: 57-66.
3 结论 [13] RAFIEE Z, BARZEGAR M, SAHARI M, et al. Nanoliposomal
carriers for improvement the bioavailability of high-valued phenolic
用磷脂-壳聚糖自组装纳米粒包埋荷叶碱，并以 compounds of pistachio green hull extract[J]. Food Chemistry, 2017,
220: 115-122.
包封率为指标探究了最佳制备工艺。结果表明，当 （下转第 2131 页）