■纳米粒子具有改善水溶性差的药物的溶解度的优点,促进药物跨越生物屏障,并减少肺部药物递送中的巨噬细胞吞噬。然而,纳米粒子具有较小的空气动力学粒径,这使得当直接递送到肺部时难以实现最佳沉积。因此,有效地将纳米颗粒输送到肺部已成为一个热门的研究课题。
纳米聚集体微粒被用作肺部药物递送策略,用于改善环孢菌素A(CsA)的生物利用度。以聚乙烯吡咯烷酮(PVP)为赋形剂,结合反溶剂法和喷雾干燥法制备纳米聚集体微粒。物理化学性质,空气动力学特性,系统评估了纳米聚集体微粒的体内药代动力学和吸入毒性。
■最佳纳米颗粒主要表现出球形,粒径和ζ电位为180.52nm和-19.8mV。纳米聚集体微粒表现出不规则形状,粒径小于1.6μm,载药量(DL)值高于70%。制剂NM-2作为最佳纳米聚集体微粒适用于肺部药物递送,可能沉积在细支气管和肺泡区域,FPF和MMAD值分别为89.62%和1.74μm。此外,吸入NM-2的Cmax和AUC0-∞值比口服环孢素软胶囊(Neoral®)高约1.7倍和1.8倍。吸入毒性研究表明,NM-2的肺部递送不会导致肺功能损伤,炎症反应,或组织损伤。
■用于肺部给药的新型纳米聚集体微粒可有效提高CsA的相对生物利用度,具有巨大的临床应用潜力。
UNASSIGNED: Nanoparticles have the advantages of improving the solubility of poorly water-soluble drugs, facilitating the drug across biological barriers, and reducing macrophage phagocytosis in pulmonary drug delivery. However, nanoparticles have a small aerodynamic particle size, which makes it difficult to achieve optimal deposition when delivered directly to the lungs. Therefore, delivering nanoparticles to the lungs effectively has become a popular research topic.
UNASSIGNED: Nanoaggregate microparticles were used as a pulmonary drug delivery strategy for the improvement of the bioavailability of cyclosporine A (CsA). The nanoaggregate microparticles were prepared with polyvinyl pyrrolidone (PVP) as the excipient by combining the anti-solvent method and spray drying process. The physicochemical properties, aerodynamic properties, in vivo pharmacokinetics and inhalation toxicity of nanoaggregate microparticles were systematically evaluated.
UNASSIGNED: The optimal nanoparticles exhibited mainly spherical shapes with the particle size and zeta potential of 180.52 nm and -19.8 mV. The nanoaggregate microparticles exhibited irregular shapes with the particle sizes of less than 1.6 µm and drug loading (DL) values higher than 70%. Formulation NM-2 as the optimal nanoaggregate microparticles was suitable for pulmonary drug delivery and probably deposited in the bronchiole and alveolar region, with FPF and MMAD values of 89.62% and 1.74 μm. In addition, inhaled NM-2 had C max and AUC0-∞ values approximately 1.7-fold and 1.8-fold higher than oral cyclosporine soft capsules (Neoral®). The inhalation toxicity study suggested that pulmonary delivery of NM-2 did not result in lung function damage, inflammatory responses, or tissue lesions.
UNASSIGNED: The novel nanoaggregate microparticles for pulmonary drug delivery could effectively enhance the relative bioavailability of CsA and had great potential for clinical application.