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pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

Acta Pharmaceutica Sinica B 2022年第2期12卷 600-620页

作者： Makhloufi Zoulikha Qingqing Xiao George Frimpong Boafo Marwa A.Sallam Zhongjian Chen Wei He Department of Pharmaceutics School of PharmacyChina Pharmaceutical UniversityNanjing 211198China Department of Industrial Pharmacy Faculty of PharmacyAlexandria UniversityAlexandria 21521Egypt Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China

The use of small interfering RNAs(si RNAs)has been under investigation for the treatment of several unmet medical needs,including acute lung injury/acute respiratory distress syndrome(ALI/ARDS)wherein si RNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the m RNA level.The properties such as clear anatomy,accessibility,and relatively low enzyme activity make the lung a good target for local si RNA therapy.However,the translation of si RNA is restricted by the inefficient delivery of si RNA therapeutics to the target cells due to the properties of naked si RNA.Thus,this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable si RNA formulations for human use before si RNA therapeutics for ALI/ARDS become available in the clinic.

关键词： pulmonary administration Drug delivery Nanoparticles siRNA Cellular uptake Endosomal escape Inflammatory diseases ALI/ARDS

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Salvianolic acid B dry powder inhaler for the treatment of idiopathic pulmonary fibrosis

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Asian Journal of Pharmaceutical Sciences 2022年第3期17卷 447-461页

作者： Peng Lu Jiawei Li Chuanxin Liu Jian Yang Hui Peng Zhifeng Xue Zhidong Liu State Key Laboratory of Component-Based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique Ministry of EducationTianjin 301617China Haihe Laboratory of Modern Chinese Medicine Tianjin 301617China College of Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Pharmacy Suzhou TCM Hospital Affiliated to Nanjing University of Chinese MedicineSuzhouJiangsu 215009China Endocrine and Metabolic Disease Center The First Affiliated Hospitaland College of Clinical Medicine of Henan University of Science and TechnologyMedical Key Laboratory of Hereditary Rare Diseases of HenanLuoyang Sub-center of National Clinical Research Center for Metabolic DiseasesLuoyangHenan 471003China.

Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.

关键词： Salvianolic acid B Dry powder inhaler Idiopathic pulmonary fibrosis pulmonary administration

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