AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Department of Biomaterials and Composites, Al. Mickiewicza 30, 30-059 Kraków, Poland.
Silesian University of Technology, Faculty of Chemistry, Department of Physical Chemistry and Technology of Polymers, ul. M. Strzody 9, 44-100 Gliwice, Poland.
Biomater Adv. 2023 Oct;153:213540. doi: 10.1016/j.bioadv.2023.213540. Epub 2023 Jun 28.
Recurrent bacterial infections are a common cause of death for patients with cystic fibrosis and chronic obstructive pulmonary disease. Herein, we present the development of the degradable poly(sebacic acid) (PSA) microparticles loaded with different concentrations of azithromycin (AZ) as a potential powder formulation to deliver AZ locally to the lungs. We characterized microparticle size, morphology, zeta potential, encapsulation efficiency, interaction PSA with AZ and degradation profile in phosphate buffered saline (PBS). The antibacterial properties were evaluated using the Kirby-Bauer method against Staphylococcus aureus. Potential cytotoxicity was evaluated in BEAS-2B and A549 lung epithelial cells by the resazurin reduction assay and live/dead staining. The results show that microparticles are spherical and their size, being in the range of 1-5 μm, should be optimal for pulmonary delivery. The AZ encapsulation efficiency is nearly 100 % for all types of microparticles. The microparticles degradation rate is relatively fast - after 24 h their mass decreased by around 50 %. The antibacterial test showed that released AZ was able to successfully inhibit bacteria growth. The cytotoxicity test showed that the safe concentration of both unloaded and AZ-loaded microparticles was equal to 50 μg/ml. Thus, appropriate physicochemical properties, controlled degradation and drug release, cytocompatibility, and antibacterial behavior showed that our microparticles may be promising for the local treatment of lung infections.
复发性细菌感染是囊性纤维化和慢性阻塞性肺疾病患者死亡的常见原因。在此，我们介绍了可生物降解的聚（癸二酸）（PSA）载不同浓度阿奇霉素（AZ）微球的开发，作为一种潜在的粉末制剂，将 AZ 局部递送至肺部。我们对微球的粒径、形态、Zeta 电位、包封效率、PSA 与 AZ 的相互作用以及在磷酸盐缓冲盐水（PBS）中的降解情况进行了表征。采用 Kirby-Bauer 法对抗金黄色葡萄球菌评估了抗菌性能。通过 Resazurin 还原试验和死活染色法，在 BEAS-2B 和 A549 肺上皮细胞中评估了潜在的细胞毒性。结果表明，微球呈球形，粒径在 1-5 μm 范围内，应为肺部给药的最佳粒径。所有类型的微球的 AZ 包封效率均接近 100%。微球的降解速率相对较快 - 24 小时后，其质量减少了约 50%。抗菌试验表明，释放的 AZ 能够成功抑制细菌生长。细胞毒性试验表明，未加载和加载 AZ 的微球的安全浓度均等于 50 μg/ml。因此，适当的物理化学性质、可控的降解和药物释放、细胞相容性和抗菌行为表明，我们的微球可能有望用于肺部感染的局部治疗。
