PEG包衣左氧氟沙星脂质体的制备及性质

doi:10.6040/j.issn.1671-7554.0.2017.339

山东大学学报（医学版） ›› 2017, Vol. 55 ›› Issue (8): 42-47.doi: 10.6040/j.issn.1671-7554.0.2017.339

PEG包衣左氧氟沙星脂质体的制备及性质

张新科¹,陈英²,李鹏³,陈洪元⁴,黄桂华⁵

1.山东大学药学院新药筛选平台, 山东济南 250012;2.日照市人民医院妇产科, 山东日照 276826;3.山东省环境保护科学研究设计院, 山东济南 250013;4.山东大学附属省立医院普外科, 山东济南 250021;5.山东大学药学院药物制剂研究所, 山东济南 250012

收稿日期:2017-04-19 出版日期:2017-08-10 发布日期:2017-08-10
通讯作者: 黄桂华. E-mail:hghyj@sdu.edu.cn E-mail:hghyj@sdu.edu.cn

Preparation and characterization of PEG coating levofloxacin-liposomes

ZHANG Xinke¹, CHEN Ying², LI Peng³, CHEN Hongyuan⁴, HUANG Guihua⁵

1. Drug Screening Platform, School of Pharmaceutical Science, Shandong University, Jinan 250012, Shandong, China;
2. Department of Gynaecology and Obstetrics, Rizhao Municipal Peoples Hospital, Rizhao 276826, Shandong, China;
3. Shandong Academy of Environmental Science, Jinan 250013, Shandong, China;
4. Department of General Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
5.Institute of Pharmaceutics, School of Pharmaceutical Science, Shandong University, Jinan 250012, Shandong, China

Received:2017-04-19 Online:2017-08-10 Published:2017-08-10

摘要/Abstract

摘要： 目的制备PEG2000包衣左氧氟沙星脂质体,并对其理化性质、初步稳定性及动力学特性进行评价。方法选用硫酸铵梯度法制备左氧氟沙星脂质体,以包封率及稳定性为指标筛选PEG2000包衣左氧氟沙星脂质体的最佳制备工艺;采用透射显微镜观察脂质体的外观形态;电位激光粒度分析仪测定粒径及表面Zeta电位;动态膜透析法测定脂质体体外释药特性;对其初步稳定性进行考察;对其体内药动学进行研究。结果 PEG2000包衣左氧氟沙星脂质体形态圆整,粒径分布均匀,包封率为(77.97±1.09)%,稳定性及体内外缓释性能均好于未包衣左氧氟沙星脂质体。结论构建的PEG包衣左氧氟沙星脂质体能明显改善脂质体的稳定性,能为提高脂质体的贮存稳定性开辟一条新途径。

关键词: 硫酸铵梯度法, PEG包衣, 肺靶向脂质体, 稳定性, 左氧氟沙星

Abstract: Objective PEG2000 was used to coat levofloxacin-liposomes(Lvf-lips)in order to improve the stability. The physico-chemical property, preliminary stability and pharmacokinetics of PEG 2000 coating levofloxacin-liposome(PEG Lvf-lips)were systematically investigated. Methods Lvf-lips were prepared by ammonium sulfate gradients method, and the optimal preparation technique of PEG Lvf-lips was screened based on the entrapment efficiency and preliminary stability. The properties of PEG Lvf-lips, such as morphology, diameter and size distribution, were observed with transmission electric microscope, laser dispersive analyzing and micro-electrophoresis apparatus. In vitro drug release of PEG Lvf-lips was performed with the dialysis bag diffusion technique. The pharmacokinetics property was also studied. Results PEG Lvf-lips had spherical shapes and uniform particle size. The entrapment efficiency was(77.97±1.09)%. The stability and sustained release effects in vitro and in vivo PEG Lvf-lips were superior to non-PEG coating liposomes. Conclusion PEG 2000 coating can significantly improve the stability of Lvf-lips, which provides a new pathway for liposome stability.

Key words: Levofloxacin, Pulmonary targeted liposome, Ammonium sulfate gradients method, PEG coating, Stability

中图分类号:

R944.9

张新科,陈英,李鹏,陈洪元,黄桂华. PEG包衣左氧氟沙星脂质体的制备及性质[J]. 山东大学学报（医学版）, 2017, 55(8): 42-47.

ZHANG Xinke, CHEN Ying, LI Peng, CHEN Hongyuan, HUANG Guihua. Preparation and characterization of PEG coating levofloxacin-liposomes[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(8): 42-47.

参考文献

[1] Lee HK, DeVito V, Vercelli C, et al. Ex vivo antibacterial activity of levofloxacin against Escherichia coli and its pharmacokinetic profile following intravenous and oral administrations in broilers[J]. Res Vet Sci, 2017, 112(1): 26-33.
[2] Elborn JS, Vataire AL, Fukushima A, et al. Comparison of inhaled antibiotics for the treatment of chronic pseudomonas aeruginosa lung infection in patients with cystic fibrosis: systematic literature review and network meta-analysis[J]. Clin Ther, 2016, 38(10): 2204-2226.
[3] Gong X, Wang H, Yuan Y. Analysis of the first therapeutic-target-achieving time of warfarin therapy and associated factors in patients with pulmonary embolism[J]. Exp Ther Med, 2016, 12(4): 2265-2274.
[4] Matsuse H, Oshio T, Kishimoto K, et al. A case of pulmonary mycobacterium abscessus infection that developed during immunosuppressive therapy for myasthenia gravis with recurrent thymoma[J]. Kekkaku, 2016, 91(2): 53-57.
[5] 张菁, 郁继诚, 施耀国, 等. 左氧氟沙星药代动力学/药效学研究[J]. 中华医学杂志, 2005, 27: 1926-1932. ZHANG Jing, YU Jicheng, SHI Yaoguo, et al. Study of pharmacokinetics/pharmacodymics os levofloxacin[J]. Natl Med J China, 2005, 27: 1926-1932.
[6] Fresta M, Spadaro A, Cerniglia G, et al. Intracellular accumulation of ofloxacin-loaded liposomes in human synovial fibroblasts[J]. Antimicrob Agents Chemother, 1995, 39(6): 1372-1375.
[7] Ghimire S, Van't Boveneind-Vrubleuskaya N, Akkerman OW, et al. Pharmacokineti /pharmacodynamic-based optimization of levofloxacin administration in the treatment of MDR-TB[J]. J Antimicrob Chemother, 2016, 71(10): 2691-2703.
[8] Elborn JS, Flume PA, Cohen F, et al. Safety and efficacy of prolonged levofloxacin inhalation solution(APT-1026)treatment for cystic fibrosis and chronic Pseudomonas aeruginosa airway infection[J]. J Cyst Fibros, 2016, 15(5): 634-640.
[9] Gaspar MC, Gregoire N, Sousa JJ, et al. Pulmonary pharmacokinetics of levofloxacin in rats after aerosolization of immediate-release chitosan or sustained-release PLGA microspheres[J]. Eur J Pharm Sci, 2016, 93(1): 184-191.
[10] Propst CN, Nwabueze AO, Kanev IL, et al. Nanoaerosols reduce required effective dose of liposomal levofloxacin against pulmonary murine Francisella tularensis subsp. novicida infection[J]. J Nanobiotechnology, 2016, 14(1): 29-38.
[11] Islan GA, Tornello PC, Abraham GA, et al. Smart lipid nanoparticles containing levofloxacin and DNase for lung delivery. Design and characterization[J]. Colloids Surf B Biointerfaces, 2016, 143(1): 168-176.
[12] 樊菊香, 吴国球, 严雪娇, 等. 靶向左氧氟沙星脂质体的制备及其抗耐药菌作用的研究[J]. 东南大学学报(医学版), 2015, 34(1): 27-31. FAN Juxiang, WU Guoqiu, YAN Xuejiao, et al. Study on targeting levofloxacin liposome against drug-resistance bacteria and its preparation[J]. J Southeast Uni(Medical Science Edition), 2015, 34(1): 27-31.
[13] Zhang X, Sun P, Bi R, et al. Targeted delivery of levofloxacin-liposomes for the treatment of pulmonary inflammation[J]. J Drug Target, 2009, 17(5): 399-407.
[14] 张新科. 左氧氟沙星脂质体的肺靶向性研究[D]. 济南:山东大学, 2009.
[15] Elhissi A. Liposomes for pulmonary drug delivery: the role of formulation and inhalation device design[J]. Curr Pharm Des, 2017, 23(3): 362-372.
[16] Hussain S. Nanomedicine for treatment of lung cancer[J]. Adv Exp Med Biol, 2016, 890(1): 137-147.
[17] Zaru M, Sinico C, De Logu A, et al. Rifampicin-loaded liposomes for the passive targeting to alveolar macrophages: in vitro and in vivo evaluation[J]. J Liposome Res, 2009, 19(1): 68-76.
[18] Gubernator J. Active methods of drug loading into liposomes: recent strategies for stable drug entrapment and increased in vivo activity[J]. Expert Opin Drug Deliv, 2011, 8(5): 565-580.
[19] Tahara K, Tomida H, Ito Y, et al. Pulmonary liposomal formulations encapsulated procaterol hydrochloride by a remote loading method achieve sustained release and extended pharmacological effects[J]. Int J Pharm, 2016, 505(1-2): 139-146.
[20] Blume G, Cevc G. Liposomes for the sustained drug release in vivo[J]. Biochim Biophys Acta, 1990, 1029(1): 91-97.
[21] Wu NZ, Da D, Rudoll TL, et al. Increased microvascular permeability contributes to preferential accumulation of Stealth liposomes in tumor tissue[J]. Cancer Res, 1993, 53(16): 3765-3770.
[22] Gabizon A, Catane R, Uziely B, et al. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes[J]. Cancer Res, 1994, 54(4): 987-992.
[23] Jain NK, Nahar M. PEGylated nanocarriers for systemic delivery[J]. Methods Mol Biol, 2010, 624: 221-234. doi: 10.1007/978-1-60761-609-2_15.
[24] Suk JS, Xu QG, Kim N, et al. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery[J]. Adv Drug Deliv Rev, 2016, 99(PtA): 28-51. doi: 10.1016/j.addr.2015.09.012.
[25] Dadashzadeh S, Mirahmadi N, Babaei MH, et al. Peritoneal retention of liposomes: Effects of lipid composition PEG coating and liposome charge[J]. J Control Release, 2010, 148(2): 177-186.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed

PEG包衣左氧氟沙星脂质体的制备及性质

Preparation and characterization of PEG coating levofloxacin-liposomes

PDF (PC)

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 4

多维度评价

本文评价

推荐阅读 0

[1]	常飞,姜宝岐,董作青,刘佳,徐欣. 关于初期稳定性对即刻种植成功率影响的动物实验研究[J]. 山东大学学报（医学版）, 2017, 55(3): 54-58.
[2]	朱建峰. 盐酸左氧氟沙星治疗细菌性结膜炎的疗效观察[J]. 山东大学学报（医学版）, 2014, 52(S1): 135-135.
[3]	曹见敏1，张蕾1，郭斌2. 魟鱼软骨多糖眼用纳米乳的质量评价[J]. 山东大学学报(医学版), 2010, 48(5): 157-160.
[4]	高扬，单宁宁，李心河，刘延红，夏洪印，王慧敏 . 自制质控血清的临床应用评估[J]. 山东大学学报(医学版), 2009, 47(04): 72-74.