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两性霉素B负载的聚乳酸-羟基乙酸共聚物-聚乙二醇-半乳糖胺纳米粒的制备、理化性质表征及抗真菌评价

Preparation, Physicochemical Characterization and Anti-Fungal Evaluation of Amphotericin B-Loaded PLGA-PEG-Galactosamine Nanoparticles.

作者信息

Mohammadi Ghobad, Fathian-Kolahkaj Mostafa, Mohammadi Pardis, Adibkia Khosro, Fattahi Ali

机构信息

Pharmaceutical Sciences Research Center Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Adv Pharm Bull. 2021 Feb;11(2):311-317. doi: 10.34172/apb.2021.044. Epub 2020 Jul 15.

Abstract

The present study aimed to formulate PLGA and PLGA-PEG-galactosamine nanoparticles (NPs) loaded with amphotericin B with appropriate physicochemical properties and antifungal activity. PLGA was functionalized with GalN to increase the adhesion and antifungal activity of NPs against . The physicochemical properties of NPs were characterized by particle size determination, zeta potential, drug crystallinity, loading efficiency, dissolution studies, differential scanning calorimeter (DSC), X-ray powder diffraction (XRPD), and Fourier transform infrared (FT-IR). Antifungal activity of the NPs at different drug/polymer ratios was examined by determining minimum inhibitory concentrations (MICs). the FT-IR and HNMR analysis successfully confirmed the formation of PLGA- PEG-GalN NPs. The NPs were in the size range of 174.1 ± 3.49 to 238.2±7.59 nm while PLGA-GalN NPs were 255.6 ±4.08 nm in size , respectively. Loading efficiency was in the range of 67%±2.4 to 77%±1.6, and entrapment efficiency in the range of 68.185%±1.9 to 73.05%±0.6. Zeta potential and loading efficiency for PLGA-GalN NPs were -0.456, 71%. The NPs indicated an amorphous status according to XRPD patterns and DSC thermograms. The PLGA-PEG-GalN NPs showed higher fungistatic activity than PLGA NPs. the results demonstrated that the antifungal activity of PLGA-PEG-GalN NPs was higher than pure amphotericin B and PLGA NPs.

摘要

本研究旨在制备负载两性霉素B且具有适当理化性质和抗真菌活性的聚乳酸-羟基乙酸共聚物(PLGA)及聚乳酸-羟基乙酸共聚物-聚乙二醇-半乳糖胺纳米粒(NPs)。用半乳糖胺(GalN)对PLGA进行功能化修饰,以提高纳米粒对……的黏附性和抗真菌活性。通过粒径测定、zeta电位、药物结晶度、载药效率、溶出度研究、差示扫描量热法(DSC)、X射线粉末衍射(XRPD)和傅里叶变换红外光谱(FT-IR)对纳米粒的理化性质进行表征。通过测定最低抑菌浓度(MICs)来检测不同药物/聚合物比例下纳米粒的抗真菌活性。FT-IR和1H NMR分析成功证实了PLGA-PEG-GalN纳米粒的形成。纳米粒的粒径范围为174.1±3.49至238.2±7.59 nm,而PLGA-GalN纳米粒的粒径分别为255.6±4.08 nm。载药效率在67%±2.4至77%±1.6范围内,包封率在68.185%±1.9至73.05%±0.6范围内。PLGA-GalN纳米粒的zeta电位和载药效率分别为-0.456和71%。根据XRPD图谱和DSC热谱图,纳米粒呈现无定形状态。PLGA-PEG-GalN纳米粒显示出比PLGA纳米粒更高的抑菌活性。结果表明,PLGA-PEG-GalN纳米粒的抗真菌活性高于纯两性霉素B和PLGA纳米粒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/408c/8046404/505c4e1266d8/apb-11-311-g001.jpg

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