Department of Formulation Design and Pharmaceutical Technology, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Department of Pathobiochemistry, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Eur J Pharm Biopharm. 2021 Oct;167:116-126. doi: 10.1016/j.ejpb.2021.07.017. Epub 2021 Aug 5.
This study aimed to design dry powder inhaler formulations using a hydrophilic polymeric polysaccharide, phytoglycogen (PyG), as a multi-functional additive that increases the phagocytic activity of macrophage-like cells and enhances pulmonary delivery of drugs. The safety and usefulness of PyG were determined using in vitro cell-based studies. Dry powder inhaler formulations of an antitubercular drug, rifampicin, were fabricated by spray drying with PyG. The cytotoxicity, effects on phagocytosis, particle size, and morphology were evaluated. The aerosolization properties of the powder formulations were evaluated using an Andersen cascade impactor (ACI). Scanning electron microscope images of the particles on each ACI stage were captured to observe the deposition behavior. PyG showed no toxicity in A549, Calu-3, or RAW264.7 cell lines. At concentrations of 0.5 and 1 g/L, PyG facilitated the cellular uptake of latex beads and the expression of pro-inflammatory cytokine genes in RAW264.7 cells. Formulations with outstanding inhalation potential were produced. The fine particle fraction (aerodynamic size 2-7 µm) of the porous particle batch reached nearly 60%, whereas in the formulation containing wrinkled carrier particles, the extra-fine particle fraction (aerodynamic particle size < 2 μm) was 25.0% ± 1.7%. The deposition of porous and wrinkled particles on individual ACI stages was distinct. The inclusion of PyG dramatically improved the inhalation performance of porous and wrinkled powder formulations. These easily inhaled immunostimulatory carrier particles may advance the state of research by enhancing the therapeutic effect and alveolar delivery of antitubercular drugs.
本研究旨在设计干粉吸入剂制剂，使用亲水性聚合多糖植物糖原（PyG）作为多功能添加剂，提高巨噬细胞样细胞的吞噬活性，并增强药物的肺部传递。使用基于细胞的体外研究来确定 PyG 的安全性和有用性。通过喷雾干燥用 PyG 制备抗结核药物利福平的干粉吸入剂制剂。评估了细胞毒性、吞噬作用、粒径和形态的影响。使用安德森级联撞击器（ACI）评估粉末制剂的空气动力学特性。捕获每个 ACI 级别的颗粒的扫描电子显微镜图像，以观察沉积行为。PyG 在 A549、Calu-3 或 RAW264.7 细胞系中没有显示出毒性。在 0.5 和 1 g/L 的浓度下，PyG 促进了 RAW264.7 细胞中乳胶珠的细胞摄取和促炎细胞因子基因的表达。生产了具有出色吸入潜力的制剂。多孔颗粒批次的细颗粒分数（空气动力学粒径 2-7 µm）接近 60%，而在含有皱缩载体颗粒的制剂中，超细颗粒分数（空气动力学粒径 < 2 µm）为 25.0%±1.7%。多孔和皱缩颗粒在各个 ACI 级上的沉积明显不同。PyG 的包含极大地改善了多孔和皱缩粉末制剂的吸入性能。这些易于吸入的免疫刺激性载体颗粒可能通过增强抗结核药物的治疗效果和肺泡传递来推动研究进展。
