用于非囊性纤维化支气管扩张症治疗的环丙沙星吸入式纳米结构脂质载体的研制。
Development of Inhalable Nanostructured Lipid Carriers for Ciprofloxacin for Noncystic Fibrosis Bronchiectasis Treatment.
机构信息
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Drug Regulatory Affairs, Novartis, Riyadh, Saudi Arabia.
出版信息
Int J Nanomedicine. 2021 Mar 25;16:2405-2417. doi: 10.2147/IJN.S286896. eCollection 2021.
PURPOSE
Ciprofloxacin (CIP) has poor lung targeting after oral inhalation. This study developed optimized inhalable nanostructured lipid carriers (NLCs) for CIP to enhance deposition and accumulation in deeper parts of the lungs for treatment of noncystic fibrosis bronchiectasis (NCFB).
METHODS
NLC formulations based on stearic acid and oleic acid were successfully prepared by hot homogenization and in vitro-characterized. CIP-NLCs were formulated into nanocomposite micro particles (NCMPs) for administration in dry powder inhalation (DPI) formulations by spray-drying (SD) using different ratios of chitosan (CH) as a carrier. DPI formulations were evaluated for drug content and in vitro deposition, and their mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD), and emitted dose (ED) were determined.
RESULTS
The CIP-NLCs were in the nanometric size range (102.3 ± 4.6 nm), had a low polydispersity index (0.267 ± 0.12), and efficient CIP encapsulation (98.75% ± 0.048%), in addition to a spherical and smooth shape with superior antibacterial activity. The in vitro drug release profile of CIP from CIP-NLCs showed 80% release in 10 h. SD of CIP-NLCs with different ratios of CH generated NCMPs with good yield (>65%). The NCMPs had a corrugated surface, but with increasing lipid:CH ratios, more spherical, smooth, and homogenous NCMPs were obtained. In addition, there was a significant change in the FPF with increasing lipid:CH ratios ( ˂ 0.05). NCMP-1 (lipid:CH = 1:0.5) had the highest FPD (45.0 µg) and FPF (49.2%), while NCMP-3 (lipid:CH = 1:1.5) had the lowest FPF (37.4%). All NCMP powders had an MMAD in the optimum size range of 3.9-5.1 μm.
CONCLUSION
Novel inhalable CIP NCMP powders are a potential new approach to improved target ability and delivery of CIP for NCFB treatment.
目的
口服吸入环丙沙星（CIP）后肺部靶向性差。本研究开发了优化的可吸入纳米结构化脂质载体（NLC）用于 CIP，以增强在肺部更深部位的沉积和积累，用于治疗非囊性纤维化支气管扩张症（NCFB）。
方法
基于硬脂酸和油酸的 NLC 配方通过热匀化成功制备，并进行了体外表征。CIP-NLC 被制成纳米复合微颗粒（NCMP），通过喷雾干燥（SD）用不同比例的壳聚糖（CH）作为载体制成干粉吸入（DPI）制剂。对 DPI 制剂进行药物含量和体外沉积评估，并测定其质量中值空气动力学直径（MMAD）、细颗粒分数（FPF）、细颗粒剂量（FPD）和发射剂量（ED）。
结果
CIP-NLC 的尺寸在纳米范围内（102.3 ± 4.6nm），具有低的多分散指数（0.267 ± 0.12），CIP 包封效率高（98.75% ± 0.048%），呈球形且表面光滑，具有优异的抗菌活性。CIP-NLC 体外药物释放曲线显示 10h 内释放 80%的 CIP。用不同比例 CH 的 SD 生成 CIP-NLC 的 NCMP 产率良好（>65%）。NCMP 具有波纹状表面，但随着脂质：CH 比例的增加，获得了更多球形、光滑和均匀的 NCMP。此外，随着脂质：CH 比例的增加，FPF 有显著变化（<0.05）。NCMP-1（脂质：CH = 1:0.5）的 FPD（45.0µg）和 FPF（49.2%）最高，而 NCMP-3（脂质：CH = 1:1.5）的 FPF（37.4%）最低。所有 NCMP 粉末的 MMAD 均在 3.9-5.1μm 的最佳粒径范围内。
结论
新型吸入性 CIP NCMP 粉末是提高 CIP 靶向能力和输送能力以治疗 NCFB 的新方法。
Zotero 插件