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伏立康唑载药脂质纳米粒的研制与表征

Development and characterization of the voriconazole loaded lipid-based nanoparticles.

作者信息

Füredi Petra, Pápay Zsófia Edit, Kovács Kristóf, Kiss Borbála Dalmadi, Ludányi Krisztina, Antal István, Klebovich Imre

机构信息

Semmelweis University, Department of Pharmaceutics, H-1092 Budapest Hőgyes Endre St 7., Hungary.

Semmelweis University, Department of Pharmaceutics, H-1092 Budapest Hőgyes Endre St 7., Hungary.

出版信息

J Pharm Biomed Anal. 2017 Jan 5;132:184-189. doi: 10.1016/j.jpba.2016.09.047. Epub 2016 Oct 1.

Abstract

The number of topical fungal infections is growing, mostly owing to immunosuppressive therapy. Several topical fungal infections, such as eye mycoses, can be treated by local administration of antimycotic drugs. One major group of the antifungal agents is triazole, such as voriconazole (VCZ), which is used as the first line treatment of aspergillosis. A disadvantage of VCZ is its low water solubility making the drug difficult to administer in a liquid preparation. The lipid-based nanoparticles (LNP) have attracted increasing attention due to their advantageous properties. Contrarily to the conventional carrier systems, LNP can improve the poor solubility of topically used drugs, such as VCZ. Therefore, LNP represents promising alternatives to traditional carrier systems. The aim of the study was to formulate VCZ loaded lipid-based nanoparticles (VCZ-LNP) by high pressure homogenization (HPH). The developed LNPs were characterized by particle size analysis, IR spectroscopy, differential scanning calorimetry, dialysis test and antifungal efficacy studies. The particle size of the optimized nanoparticles from the selected lipid base, Witepsol W35, was 182±4.1nm after five cycles of homogenization at 600bar. The antifungal study confirmed that the optimized VCZ-LNP inhibited the fungus reproduction.

摘要

局部真菌感染的数量正在增加,主要是由于免疫抑制治疗。一些局部真菌感染,如眼部真菌病,可以通过局部应用抗真菌药物来治疗。抗真菌药物的一个主要类别是三唑类,如伏立康唑(VCZ),它被用作曲霉病的一线治疗药物。VCZ的一个缺点是其水溶性低,使得该药物难以制成液体制剂给药。基于脂质的纳米颗粒(LNP)因其有利的特性而受到越来越多的关注。与传统的载体系统相反,LNP可以改善局部使用药物(如VCZ)的低溶解性。因此,LNP是传统载体系统有前景的替代物。本研究的目的是通过高压均质法(HPH)制备负载VCZ的基于脂质的纳米颗粒(VCZ-LNP)。通过粒度分析、红外光谱、差示扫描量热法、透析试验和抗真菌功效研究对所制备的LNP进行了表征。在600巴压力下进行五次均质循环后,从选定的脂质基质Witepsol W35制备的优化纳米颗粒的粒径为182±4.1nm。抗真菌研究证实,优化后的VCZ-LNP抑制了真菌繁殖。

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