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用于有效治疗特发性肺纤维化的脂质体干粉吸入剂配方的肺部给药

Pulmonary delivery of liposomal dry powder inhaler formulation for effective treatment of idiopathic pulmonary fibrosis.

作者信息

Chennakesavulu S, Mishra A, Sudheer A, Sowmya C, Suryaprakash Reddy C, Bhargav E

机构信息

Pharmacy Department, NDDS Laboratory, Donors Plaza, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Gujarat, India.

Pharmacology Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Gujarat, India.

出版信息

Asian J Pharm Sci. 2018 Jan;13(1):91-100. doi: 10.1016/j.ajps.2017.08.005. Epub 2017 Aug 18.

Abstract

Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide (BUD) and Colchicine (COL) liposomes were prepared by thin layer film hydration method (TFH) using 1,2-Dipalmitoyl-sn-glycero-3- phosphoglycerol sodium (DPPG), Hydrogenated Soyaphosphotidylcholine (HSPC), Soyaphosphatidylcholine (SPC), cholesterol (CHOL) and drug in different weight ratios. The optimum lipid composition for BUD (74.22 ± 0.97%) was DPPG: HSPC: CHOL (4:5:1) and for COL (50.94 ± 2.04%) was DPPG: SPC: CHOL (3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency (97.89 - 98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler (DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2 (86.53 ± 1.9%), Colchicine DPI Formulation C2 (90.54 ± 2.3 %) and BUD and COL DPI Combination M2 (89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal dry powder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at (25 °C ± 2 °C, 60% ± 5% RH) and refrigerated conditions (2 - 8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.

摘要

制备了干粉吸入剂脂质体,以研究秋水仙碱和布地奈德经肺部给药治疗特发性肺纤维化的有效性。采用薄膜水化法(TFH),使用1,2-二棕榈酰-sn-甘油-3-磷酸甘油钠(DPPG)、氢化大豆磷脂酰胆碱(HSPC)、大豆磷脂酰胆碱(SPC)、胆固醇(CHOL)和不同重量比的药物制备布地奈德(BUD)和秋水仙碱(COL)脂质体。布地奈德(74.22±0.97%)的最佳脂质组成为DPPG:HSPC:CHOL(4:5:1),秋水仙碱(50.94±2.04%)的最佳脂质组成为DPPG:SPC:CHOL(3:6:1)。这些组合物能使药物保留更长时间,因此被选作进一步研究。发现脂质体呈球形,平均尺寸低于100nm。以甘露醇作为载体和冷冻保护剂冻干的脂质体显示出高包封率(97.89 - 98.6%)。通过安德森级联撞击器分散粉末,以评估雾化粉末的性能。发现制备的脂质体干粉吸入剂(DPI)可持续释药长达24小时。优化后的布地奈德DPI制剂B2(86.53±1.9%)、秋水仙碱DPI制剂C2(90.54±2.3%)以及布地奈德和秋水仙碱DPI组合M2(89.91±1.8%,91.23±1.9%)。组织病理学结果、肺羟脯氨酸含量测定、髓过氧化物酶活性表明,脂质体干粉吸入剂给药可减轻博来霉素诱导的肺纤维化。长期稳定性研究表明,冻干的布地奈德和秋水仙碱脂质体在(25°C±2°C,60%±5%RH)和冷藏条件(2 - 8°C)下可稳定保存6个月。这些结果支持布地奈德和秋水仙碱脂质体干粉吸入剂经肺部给药治疗特发性肺纤维化,在靶部位具有延长的药物保留时间并减少全身暴露。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ad/7032187/10121b33ab2f/ajps461-ga-5001.jpg

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