目的 考察磺胺醋酰-氧氟沙星脂质体制备工艺中的各因素影响以及药物的抗菌活性。方法 采用薄膜分散-超声法制备磺胺醋酰-氧氟沙星脂质体,电子显微镜观察脂质体粒径,过滤法分离游离药物,紫外线(UV)测定包封率,微孔显色法测定其抗菌活性。采用单因素实验来考察脂质体成膜时水浴温度、水浴时间和磷脂比对脂质体包封率以及回收率的影响,确定最佳的制备工艺。结果 电子显微镜结果显示,脂质体形态良好,粒径较大的脂质体可明显看到指纹状结构,确定此为多室脂质体。确定磺胺醋酰-氧氟沙星脂质体的较优工艺条件为水浴温度45 ℃,水浴时间3 h,磷脂比6∶1。抗菌活性结果表明,空白脂质体没有抗菌活性,杂合药物分子有明显的抗菌活性。结论 将杂合抗菌分子制作成脂质体能够较好地保护杂合分子,为新剂型的设计奠定了良好基础。
Abstract
OBJECTIVE To investigate the influence of various factors in the preparation process of sulfacetamide-ofloxacin liposomes and the antibacterial activity of the drug. METHODS The sulfacetamide-ofloxacin liposomes were prepared by the thin film dispersion-ultrasonic method, the liposomes size were observed by electron microscope, the free drugs were separated by filtration, the encapsulation efficiency was measured by UV spectrophotometry, and the antibacterial activity was measured by microporous chromogenic method. Based on the from single factor tests, orthogonal experimental design was used to investigate the influence of water bath temperature, water bath time and phospholipid ratio on the encapsulation efficiency of liposomes during film formation to determine the best preparation process. RESULTS The results of electron microscopy showed that the liposomes had good morphology, and the fingerprint-like structure could be clearly seen in the liposomes with larger particle size, which confirmed that the liposomes were multilamellar liposomes. The optimal technological conditions for determining sulfacetamide-ofloxacin liposomes were as follows: water bath temperature: 45 ℃, water bath time: 3h, and phospholipid ratio 6∶1. The results of antibacterial activity showed that the blank liposome had no antibacterial activity, and the hybrid drug molecule had obvious antibacterial activity. CONCLUSION The production of hybrid antibacterial molecules into liposomes can better protect the hybrid molecules, laying a good foundation for the design of new dosage forms.
关键词
磺胺醋酰-氧氟沙星脂质体 /
薄膜分散-超声法 /
磷脂比 /
杂合分子 /
抗菌活性
{{custom_keyword}} /
Key words
sulfacetamide-ofloxacin liposome /
film dispersion-ultrasonic method /
phospholipid ratio /
hybrid molecule /
antibacterial activity
{{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] MIGLIORI G B, SOTGIU G, ROSALES-KLINTZ S, et al. ERS/ECDC Statement: European Union standards for tuberculosis care, 2017 update [J]. Eur Respir J, 2018, 51(5): 1-18.
[2] MABHULA A, SSINGH V. Drug-resistance in Mycobacterium tuberculosis: where we stand [J]. Med Chem Comm, 2019, 10:1342-1360.
[3] RONALD L A, CAMPBELL J R, CAREN R, et al. Estimated impact of World Health Organization latent tuberculosis screening guidelines in a low TB incidence: retrospective cohort study [J]. Clinl Infect Dis, 2009, 69(12):2101-2108.
[4] CHAKAYA J, KHAN M, NTOUMI F, et al. Global Tuberculosis Report 2020 - Reflections on the Global TB burden, treatment and prevention efforts[J]. Int J Infect Dis, 2021(113): s7-s12.
[5] KYU H H, MADDISON E R, HENRY N J, et al. The global burden of tuberculosis: results from the Global Burden of Disease Study 2015[J]. Lancet Infect Dis, 2018, 18(3): 261-284.
[6] GARCIA-BASTEIRO A L, BREW J, WILLANS B, et al. What is the true tuberculosis mortality burden? Differences in estimates by the World Health Organization and the Global Burden of Disease Study [J]. Int J Epidemiol, 2018,47(5):1549-1560.
[7] YAQUOBI F A, AL-ABRI S, AL-ABRI B, et al. Tuberculosis elimination: a dream or a reality? The case of Oman[J]. Eur Respir J, 2018, 51(1):1-3.
[8] LI C, TANG Y, SANG Z, et al. Discovery of napabucasin derivatives for the treatment of tuberculosis [J]. Med Chem Comm, 2019, 10(9):1635-1640.
[9] CHEN J R, SHAO L, CHEN D J. Recent advances in hybrid antibacterial agents [J]. Chin J Pharm (中国医药工业杂志), 2017, 48(9):1233-1246.
[10] DANG B, ZHANG S J. Talking about the clinical application of sulfa drugs [J]. Chin J Vet Med(中国兽医杂志), 2010, 46(12):93.
[11] LIU M, MA Y L, GANG Y G, et al. Clinical observation of levofloxacin and capreomycin combined with chemotherapy regimen in the treat-ment of multi-drug resistant tuberculosis [J]. J China Pharm(中国药房), 2016, 27:3788-3790.
[12] HEYCKENDORF J, VAN LETH F, KALSDORF B, et al. Relapse-free cure from multidrug-resistant tuberculosis in Germany[J]. Eur Respir J, 2018, 51(2): 1-4.
[13] CHEN L F, CHEN R, HUANG S P, et al. Population pharmacokinetics of isohiazid in chinese tuberculosis patients [J]. Chin Pharm J(中国药学杂志), 2017, 52(24):2185-2191.
[14] EVANS J C, MIZRAHI V. Priming the tuberculosis drug pipeline: new antimycobacterial targets and agents [J]. Curr opin microbiol, 2018, 45: 39-46.
[15] SUN H P, ZAHNG G X, CHENG G, et al. Manufacturing and clinical application of liposomal drugs [J]. Chin J Pharm (中国医药工业杂志), 2019, 50(10):1160-1171.
[16] ZHANG J J, SUN X D. Application research progress of new liposomes [J]. J China Pharm(中国药房), 2007, 18(31):2465-2466.
[17] LOIRA-PASTORIZA C, TODOROFF J, VANBEVER R. Delivery strategies for sustained drug release in the lungs[J]. Adv Drug Deliv Rev, 2014, 75(8): 81-91.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(1396 KB)
