目的 制备载高乌甲素(LA)的聚乳酸(PLA)纳米粒,考察其体外释药特性。方法 以生物可降解聚乳酸为载体材料,以聚乙烯醇(PVA)为乳化剂,采用乳化-溶剂挥发法制备载高乌甲素的聚乳酸纳米粒(高乌甲素-聚乳酸 NPs),以包封率和载药量为主要评价指标,通过正交设计实验优化其制备工艺;运用激光粒度仪测定其粒径;原子力显微镜观察其形貌;动态透析法考察其体外释药特性。结果 优化工艺制备的高乌甲素聚乳酸纳米粒外观呈圆形或类圆形,平均粒径为(429±9.19)nm,高乌甲素的包封率和载药量分别为(86.34±2.15)%,(45.85±1.34)%。体外释药研究表明,纳米粒能够连续释药15 d。结论 成功制备了高乌甲素的聚乳酸纳米粒,其包封率、载药量高,体外释药具有明显的缓释特征。
Abstract
OBJECTIVE To prepare lappaconitine (LA)-loaded polylactic acid (PLA) nanoparticles (LA/PLA NPs) and investigate its release properties in vitro.METHODS LA/PLA NPs were prepared by optimized emulsion-solvent evaporation method with biodegradable PLA as carrier material and polyvinyl alcohol (PVA) as emulsifier. The entrapment efficiency and drug loading rate of LA were used as the main evaluation indexes to optimize the preparation process by orthogonal design method. The mean particle size was measured by laser particle size analyzer; the morphology of LA/PLA NPs was observed by atomic force microscope; the in vitro release behavior was studied by dynamic dialysis.RESULTS The optimized LA/PLA NPs were spherical. The mean particle size was (429?9.19) nm, the entrapment efficiency and drug loading rate were (86.34?2.15)% and (45.85?1.34)%, respectively. The in vitro release study showed that the LA/PLA NPs could provide a continuous release of LA for 15 d.CONCLUSION LA/PLA NPs with high entrapment efficiency and drug loading rate are prepared successfully, and show sustained release effect for LA in vitro.
关键词
高乌甲素 /
聚乳酸 /
纳米粒 /
乳化-溶剂挥发法 /
正交设计
{{custom_keyword}} /
Key words
lappaconitine (LA) /
polylactic acid (PLA) /
nanoparticle /
emulsion-solvent evaporation method /
orthogonal design
{{custom_keyword}} /
中图分类号：
R944
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] AMERI A. The effects of aconitum alkaloids on the central nervous system. Prog Neurobiol,1998, 56(2):211-235. [2] XIN R H, CHENG F S, HU Z Y, et al. Research situation of lappaconitine. J Tradit Chin Vet Med(中兽医医药杂志),2009, 28 (2):74-76. [3] YU J Z, ZHANG B J, JIANG X T. Clinical application of lappaconitine hydrobromide. J Second Mil Med Univ(第二军医大学学报),2005, 26 (7):822-824. [4] AYEN W Y, KUMAR N. A systematic study on lyophilization process of polymersomes for long-term storage using doxorubicin-loaded (PEG)3-PLA nanopolymersomes. Eur J Pharm Sci, 2012, 46(5):405-414. [5] ESSA S, RABANEL J M, HILDGEN P. Effect of polyethylene glycol (PEG) chain organization on the physicochemical properties of poly (d, l-lactide) (PLA) based nanoparticles. Eur J Pharm Biopharm, 2010, 75(2):96-106. [6] JIN H, LI S, HU D, et al. Preparation of PLA-PEG nanoparticles by the solution enhanced dispersion with enhanced mass transfer using ultrasound in supercritical CO2. Powder Technol,2012, 227:17-23. [7] LU R, ZHENG X Q, DONG R. Preparation research of PLA microspheres. Technol Dev Chem Ind(化工技术与开发),2009, 38 (3):4-6, 3. [8] MENG L S, YAO X J. Preparation of polylactic acid microspheres. Appl Chem Ind(应用化工), 2011, 40 (11):1945-1947. [9] JEEVITHA D, AMARNATH K. Chitosan/PLA nanoparticles as a novel carrier for the delivery of anthraquinone:Synthesis, characterization and in vitro cytotoxicity evaluation. Colloids Surf B, 2013, 101:126-134. [10] ZHANG W, ZHANG X X. Preparation of polylactic acid microspheres containing total alkaloids of Caulis sinomenii . Chin J Pharm(中国医药工业杂志),2011, 42 (5):354-357. [11] JAIN D S, ATHAWALE R B, BAJAJ A N, et al. Poly lactic acid (PLA) nanoparticles sustain the cytotoxic action of temozolomide in C6 Glioma cells. Biomed Aging Pathol, 2013, 3(4):201-208. [12] FAGUI A E, AMIEL C. PLA Nanoparticles coated with a β-cyclodextrin polymer shell:Preparation and characterization and release kinetics of a hydrophobic compound. Int J Pharm, 2012, 436(1-2):644-651.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(1570 KB)
