کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5809650 1556162 2016 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Rifapentine-loaded PLGA microparticles for tuberculosis inhaled therapy: Preparation and in vitro aerosol characterization
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Rifapentine-loaded PLGA microparticles for tuberculosis inhaled therapy: Preparation and in vitro aerosol characterization
چکیده انگلیسی

Inhaled delivery of drugs incorporated into poly (lactic-co-glycolic acid) (PLGA) microparticles allows a sustained lung concentration and encourages phagocytosis by alveolar macrophages that harboring Mycobacterium tuberculosis. However, limited data are available on the effects of physicochemical properties of PLGA, including the monomer ratio (lactide:glycide) and molecular weight (MW) on the aerosol performance, macrophage uptake, and toxicity profile. The present study aims to address this knowledge gap, using PLGAs with monomer ratios of 50:50, 75:25 and 85:15, MW ranged 24 - 240 kDa and an anti-tuberculosis (TB) drug, rifapentine. The PLGA-rifapentine powders were produced through a solution spray drying technique. The particles were spherical with a smooth surface and a volume median diameter around 2 μm (span ~ 2). When the powders were dispersed using an Osmohaler® at 100 L/min for 2.4 s, the fine particle fraction (FPFtotal, wt.% particles in aerosol < 5 μm relative to the total recovered drug mass) was ranged between 52 and 57%, with no significant difference between the formulations. This result suggests that the monomer ratio and MW are not crucial parameters for the aerosol performance of PLGA. The phagocytosis analysis was performed using Thp-1 monocyte-derived macrophages. The highest rate of uptake was observed in PLGA 85:15 followed by 75:25 and 50:50 with about 90%, 80% and 70%, respectively phagocytosis over 4 h of exposure. Furthermore, the cytotoxicity analysis on Thp-1 and human lung adenocarcinoma epithelial cells demonstrated that PLGA concentration up to 1.5 mg/mL, regardless of the monomer composition and MW, were non-toxic. In conclusion, the monomer ratio and MW are not crucial in determining the aerosol performance and cytotoxicity profile of PLGA however, the particles with high lactide composition have a superior tendency for macrophage uptake.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 88, 10 June 2016, Pages 1-11
نویسندگان
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