Institute of Biomaterials and Tissue Engineering, Huaqiao University, Xiamen, 361021, P. R. China.
Fujian Provincial Key Laboratory of Biochemical Technology (Huaqiao University), Xiamen, 361021, P. R. China.
Adv Healthc Mater. 2019 Jun;8(12):e1800910. doi: 10.1002/adhm.201800910. Epub 2018 Oct 3.
Pulmonary delivery of drugs has attracted increasing attention in healthcare, as the lungs are an easily accessible site for noninvasive systemic delivery of drugs. Although pulmonary inhalation of porous microparticles has been shown to sustain drug delivery, there are limited reports on efficient delivery of insulin and inhalation therapy of diabetes based on supercritical carbon dioxide (SC-CO ) technology. Herein, this study reports the fabrication of insulin-loaded poly-l-lactide porous microspheres (INS-PLLA PMs) by using the SC-CO technology, and their use as an inhalation delivery system potentially for diabetes therapy. Biocompatibility and delivery efficiency of the PLLA PMs in the lungs are investigated. The PLLA PMs show negligible toxicity to lung-derived cells, resulting in no significant reduction in cell viability, as well as levels of various inflammatory mediators such as interleukin (IL)-6, IL-8, and tumor necrosis factor-α, compared with the negative control group. INS-PLLA PMs are further efficiently deposited in the trachea and the bronchi of superior lobes of the lungs, which exhibit pronounced hypoglycemic activity in induced diabetic rats. Together, the results demonstrate that the INS-PLLA PMs have a strong potential as an effective strategy for inhalation treatment of diabetes.
肺部给药在医疗保健领域引起了越来越多的关注，因为肺部是药物非侵入性全身递送的一个易于到达的部位。尽管已经证明多孔微球的肺部吸入可以持续递送药物，但基于超临界二氧化碳（SC-CO2）技术的胰岛素高效递送和糖尿病吸入治疗的报道有限。在此，本研究报告了通过 SC-CO2 技术制备载胰岛素的聚-L-乳酸多孔微球（INS-PLLA PMs），并将其用作潜在的糖尿病治疗的吸入递送系统。研究了肺部中 PLLA PMs 的生物相容性和递送效率。与阴性对照组相比，PLLA PMs 对肺源细胞几乎没有毒性，细胞活力没有明显降低，白细胞介素（IL）-6、IL-8 和肿瘤坏死因子-α等各种炎症介质的水平也没有明显降低。INS-PLLA PMs 进一步有效地沉积在诱导型糖尿病大鼠肺部上叶的气管和支气管中，表现出明显的降血糖活性。总之，这些结果表明 INS-PLLA PMs 作为糖尿病吸入治疗的有效策略具有很大的潜力。
