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Antioxidant Biodegradable Covalent Cyclodextrin Frameworks as Particulate Carriers for Inhalation Therapy against Acute Lung Injury

文献类型：期刊论文

作者He, Siyu6,7; Wu, Li7; Sun, Hongyu7; Wu, Di5; Wang, Caifen7; Ren, Xiaohong7; Shao, Qun4; York, Peter4; Tong, Jiabing3; Zhu, Jie2,5
刊名ACS APPLIED MATERIALS & INTERFACES
出版日期2022-08-31
卷号14期号:34页码:38421-38435
关键词reactive oxygen species-sensitive covalent cyclodextrin frameworks acute lung injury pulmonary drug delivery ligustrazine
ISSN号1944-8244
DOI10.1021/acsami.2c05220
通讯作者Zhu, Jie(janezhutcm@foxmail.com) ; Li, Zegeng(li6609@126.com) ; Zhang, Jiwen(jwzhang@simm.ac.cn)
英文摘要Drug therapies for acute lung injury (ALI) are far from satisfactory, primarily because drugs cannot specifically target the lungs. Direct delivery of drugs to the deep alveolar regions by inhalation administration is crucial for the treatment of ALI. However, conventional inhalable carriers such as lactose and mannitol are generally inactive. Therefore, the use of a novel pharmacologically active carrier for pulmonary delivery may produce synergetic effects in treating ALI. Considering the pathophysiological environment of ALI, which typically featured excessive reactive oxygen species (ROS) and acute inflammation, we synthesized a novel kind of biodegradable and ROS-sensitive cross-linked covalent cyclodextrin frameworks (OC-COF) with uniform inhalable particle size to treat ALI. OC-COF was devised to incorporate H2O2-scavenging peroxalate ester linkages, which could hydrolyze and eliminate ROS generated in inflammatory sites. Ligustrazine (LIG), an antioxidant and anti-inflammatory natural compound, was loaded into OC-COF and evaluated as a dry powder inhaler (LIG@OC-COF) in vitro and in vivo, showing favorable aerodynamic properties and prominent antioxidant and anti-inflammatory capacities for the synergistic effects of OC-COF and LIG. In ALI rats, inhalation of LIG@OC-COF with a one-fifth LIG dose significantly alleviated the inflammation, oxidant stress, and lung damage. Western blot analysis demonstrated that LIG@OC-COF protected the lungs by regulating the Nrf2/NF-kappa B signaling pathway. In summary, this study provides a novel ROS-responsive material as an inhalable particulate carrier for the improved treatment of ALI and other medical conditions.
WOS关键词OXIDATIVE STRESS ; PULMONARY DELIVERY ; ROS ; NANOPARTICLES ; PATHOGENESIS ; PERFORMANCE ; EXOSOMES
WOS研究方向Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:000847303200001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/302138]  
专题中国科学院上海药物研究所
通讯作者Zhu, Jie; Li, Zegeng; Zhang, Jiwen
作者单位1.Natl Inst Food & Drug Control, NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipi, Beijing 100050, Peoples R China
2.Fudan Univ, Inst Integrat Med, Shanghai 200040, Peoples R China
3.Anhui Univ Chinese Med, Affiliated Hosp 1, Hefei 230031, Peoples R China
4.Univ Bradford, Inst Pharmaceut Innovat, Bradford BD7 1DP, W Yorkshire, England
5.Anhui Univ Chinese Med, Hefei 230012, Peoples R China
6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
7.Chinese Acad Sci, Ctr Drug Delivery Syst, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 He, Siyu,Wu, Li,Sun, Hongyu,et al. Antioxidant Biodegradable Covalent Cyclodextrin Frameworks as Particulate Carriers for Inhalation Therapy against Acute Lung Injury[J]. ACS APPLIED MATERIALS & INTERFACES,2022,14(34):38421-38435.
APA He, Siyu.,Wu, Li.,Sun, Hongyu.,Wu, Di.,Wang, Caifen.,...&Zhang, Jiwen.(2022).Antioxidant Biodegradable Covalent Cyclodextrin Frameworks as Particulate Carriers for Inhalation Therapy against Acute Lung Injury.ACS APPLIED MATERIALS & INTERFACES,14(34),38421-38435.
MLA He, Siyu,et al."Antioxidant Biodegradable Covalent Cyclodextrin Frameworks as Particulate Carriers for Inhalation Therapy against Acute Lung Injury".ACS APPLIED MATERIALS & INTERFACES 14.34(2022):38421-38435.

入库方式： OAI收割

来源：上海药物研究所

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