Novel copolymers of poly(sebacic anhydride) and poly(ethylene glycol) as azithromycin carriers to the lungs

IF 5.3 2区医学 Q1 ENGINEERING, BIOMEDICAL

Biocybernetics and Biomedical Engineering Pub Date : 2025-01-01 DOI:10.1016/j.bbe.2025.01.002

Konrad Kwiecień , Karolina Knap , Rick Heida , Jonasz Czajkowski , Alan Gorter , Dorota Ochońska , Przemysław Mielczarek , Agata Dorosz , Daria Niewolik , Katarzyna Reczyńska-Kolman , Katarzyna Jaszcz , Monika Brzychczy-Włoch , Tomasz R. Sosnowski , Peter Olinga , Elżbieta Pamuła

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引用次数: 0

Abstract

By many chronic lung diseases, there is a problem of recurrent bacterial infections that require frequent usage of antibiotics. They can be more effective and cause fewer side effects when administrated directly via the pulmonary route. For such purposes, various types of inhalers are used of which dry powder inhalers (DPIs) are one of the most common. Formulations such as dry powders usually consist of an active pharmaceutical ingredient (API) and a carrier material that is supposed to provide adequate properties to deliver the bioactive molecules to the site of action, effectively. Copolymers of sebacic acid (SA) and poly(ethylene glycol) (PEG) have been regarded as suitable materials for such formulations. Here, we present a study about the manufacturing of microparticles from such materials dedicated to inhalation which have been loaded with azithromycin (AZM). The microparticles (MPs) were 0.5 to 5 µm in size, presenting either a spherical or elongated shape depending on the material type and composition. The encapsulation efficiency (EE) of the MPs were almost complete with the drug loading up to 23.1 %. The powders had fair or good flowability based on Carr’s index and Hausner ratio. Due to the presence of the drug, the tendency to agglomerate decreased. As a result, up to 90 % of the obtained powders showed diameters below 5 µm. Also, the fine particles fraction (FPF) of the chosen formulation reached 66.3 ± 4.5 % and the mass median aerodynamic diameter was 3.8 ± 0.4 µm. The microparticles degraded quickly in vitro losing up to 50 % of their mass within 24 h and up to 80 % within 96 h of their incubation in phosphate-buffered saline (PBS). They were also nontoxic up to 100 µg/ml when added to cultures of A549 and BEAS-2B lung epithelial cells as well as to rat lung tissue slices tested ex vivo. The microparticles showed bactericidal effects against various strains of Staphylococcus aureus in lower than cytotoxic concentrations.

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新型聚（癸二酸酐）和聚（乙二醇）共聚物作为肺部阿奇霉素载体

许多慢性肺部疾病都存在反复细菌感染的问题，需要经常使用抗生素。当直接经肺途径给药时，它们更有效，副作用更少。为此，使用了各种类型的吸入器，其中干粉吸入器（dpi）是最常见的吸入器之一。诸如干粉之类的制剂通常由活性药物成分（API）和载体材料组成，该载体材料应提供足够的特性，以有效地将生物活性分子递送到作用部位。己二酸（SA）和聚乙二醇（PEG）的共聚物被认为是这种配方的合适材料。在这里，我们提出了一项研究，从这些专门用于吸入的材料中制造含有阿奇霉素（AZM）的微粒。微颗粒（MPs）的尺寸为0.5至5µm，根据材料类型和组成呈现球形或细长形状。MPs的包封效率（EE）基本完全，载药量高达23.1%。根据卡尔指数和豪斯纳比，粉末具有一般或良好的流动性。由于药物的存在，凝结的倾向减少了。结果，高达90%的所得粉末的直径低于5µm。所选配方的细颗粒分数（FPF）达到66.3±4.5%，质量中位数气动直径为3.8±0.4µm。微颗粒在体外迅速降解，在24小时内损失高达50%的质量，在磷酸盐缓冲盐水（PBS）中孵育96小时内损失高达80%的质量。当添加到A549和BEAS-2B肺上皮细胞培养物以及离体测试的大鼠肺组织切片中，其毒性高达100µg/ml。在低于细胞毒浓度的条件下，微颗粒对多种金黄色葡萄球菌均有杀菌作用。

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来源期刊

Biocybernetics and Biomedical Engineering ENGINEERING, BIOMEDICAL-

CiteScore

16.50

自引率

6.20%

发文量

审稿时长

38 days

期刊介绍： Biocybernetics and Biomedical Engineering is a quarterly journal, founded in 1981, devoted to publishing the results of original, innovative and creative research investigations in the field of Biocybernetics and biomedical engineering, which bridges mathematical, physical, chemical and engineering methods and technology to analyse physiological processes in living organisms as well as to develop methods, devices and systems used in biology and medicine, mainly in medical diagnosis, monitoring systems and therapy. The Journal''s mission is to advance scientific discovery into new or improved standards of care, and promotion a wide-ranging exchange between science and its application to humans.