Qi Guo, Yuxin Lu, Xiaochen Cheng, Fengjun Xiao, Qinglin Zhang, Peng Gao, Li Du
{"title":"纳米复合材料递送肝细胞生长因子基因治疗博莱霉素诱导的大鼠肺纤维化。","authors":"Qi Guo, Yuxin Lu, Xiaochen Cheng, Fengjun Xiao, Qinglin Zhang, Peng Gao, Li Du","doi":"10.2174/1567201819666220613145417","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. There is no effective treatment for PF. Hepatocyte growth factor (HGF) has anti-inflammatory and antifibrotic effects but has limited potential owing to its short half-life.</p><p><strong>Methods: </strong>To increase the transfection efficiency of pVAX-HGF, we prepared polyethyleneiminepolyethylene glycol: polyethyleneimine/pVAX-HGF (PEG-PEI: PEI/pVAX-HGF) nanocomposite loaded with a plasmid encoding the HGF gene. The PEG-PEI:PEI/pVAX-HGF characteristics, including morphology, particle size, zeta-potential, and DNA entrapment efficiency, were investigated. The pVAX-HGF nanocomposites with low toxicity and high transfection efficiency were screened by cell viability assay and cell transfection. The antifibrotic effect of pVAX-HGF nanocomposite on PF rats induced by bleomycin (BLM) was evaluated by pulmonary function measurement, pathological examination and collagen content assay.</p><p><strong>Results: </strong>Different nanocomposites were prepared to deliver pVAX-HGF, in which mix1 (PEGPEI: PEI/pVAX-HGF) has lower potential and better entrapment ability.</p><p><strong>Peg-pei: </strong>PEI/pVAX-HGF (N/P=25) nanocomposite with low toxicity and high transfection efficiency was administered to PF rats. After treatment with mix 1/pVAX-HGF, the index of lung function(including EF50, MV, TV, PEF and PIF) in mix 1/pVAX-HGF group was higher than that of the PF group. The number of cells in BALF of the mix 1/pVAX-HGF group was significantly lower than that of the PF groups, and the content of hydroxyproline(HYP) and collagen Type I (Col-I) in the lung of the mix 1/pVAX-HGF group was much lower than that of the PF groups in the early stage. The result of pathological examination showed that rats in the mix1/pVAX-HGF group showed obviously reduced alveolar septal thickening, fewer infiltrated inflammatory cells and less collagen deposition.</p><p><strong>Conclusion: </strong>The PEG-PEI:PEI/pVAX-HGF nanocomposite can ameliorate PF induced by BLM. The pVAX-HGF nanocomposite is a latent therapeutic strategy for PF.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":"20 9","pages":"1368-1379"},"PeriodicalIF":2.8000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hepatocyte Growth Factor Delivered by Nanocomposites for Gene Therapy of Bleomycin-Induced Pulmonary Fibrosis in Rats.\",\"authors\":\"Qi Guo, Yuxin Lu, Xiaochen Cheng, Fengjun Xiao, Qinglin Zhang, Peng Gao, Li Du\",\"doi\":\"10.2174/1567201819666220613145417\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. There is no effective treatment for PF. Hepatocyte growth factor (HGF) has anti-inflammatory and antifibrotic effects but has limited potential owing to its short half-life.</p><p><strong>Methods: </strong>To increase the transfection efficiency of pVAX-HGF, we prepared polyethyleneiminepolyethylene glycol: polyethyleneimine/pVAX-HGF (PEG-PEI: PEI/pVAX-HGF) nanocomposite loaded with a plasmid encoding the HGF gene. The PEG-PEI:PEI/pVAX-HGF characteristics, including morphology, particle size, zeta-potential, and DNA entrapment efficiency, were investigated. The pVAX-HGF nanocomposites with low toxicity and high transfection efficiency were screened by cell viability assay and cell transfection. The antifibrotic effect of pVAX-HGF nanocomposite on PF rats induced by bleomycin (BLM) was evaluated by pulmonary function measurement, pathological examination and collagen content assay.</p><p><strong>Results: </strong>Different nanocomposites were prepared to deliver pVAX-HGF, in which mix1 (PEGPEI: PEI/pVAX-HGF) has lower potential and better entrapment ability.</p><p><strong>Peg-pei: </strong>PEI/pVAX-HGF (N/P=25) nanocomposite with low toxicity and high transfection efficiency was administered to PF rats. After treatment with mix 1/pVAX-HGF, the index of lung function(including EF50, MV, TV, PEF and PIF) in mix 1/pVAX-HGF group was higher than that of the PF group. The number of cells in BALF of the mix 1/pVAX-HGF group was significantly lower than that of the PF groups, and the content of hydroxyproline(HYP) and collagen Type I (Col-I) in the lung of the mix 1/pVAX-HGF group was much lower than that of the PF groups in the early stage. The result of pathological examination showed that rats in the mix1/pVAX-HGF group showed obviously reduced alveolar septal thickening, fewer infiltrated inflammatory cells and less collagen deposition.</p><p><strong>Conclusion: </strong>The PEG-PEI:PEI/pVAX-HGF nanocomposite can ameliorate PF induced by BLM. The pVAX-HGF nanocomposite is a latent therapeutic strategy for PF.</p>\",\"PeriodicalId\":10842,\"journal\":{\"name\":\"Current drug delivery\",\"volume\":\"20 9\",\"pages\":\"1368-1379\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current drug delivery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1567201819666220613145417\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current drug delivery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1567201819666220613145417","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Hepatocyte Growth Factor Delivered by Nanocomposites for Gene Therapy of Bleomycin-Induced Pulmonary Fibrosis in Rats.
Background: Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. There is no effective treatment for PF. Hepatocyte growth factor (HGF) has anti-inflammatory and antifibrotic effects but has limited potential owing to its short half-life.
Methods: To increase the transfection efficiency of pVAX-HGF, we prepared polyethyleneiminepolyethylene glycol: polyethyleneimine/pVAX-HGF (PEG-PEI: PEI/pVAX-HGF) nanocomposite loaded with a plasmid encoding the HGF gene. The PEG-PEI:PEI/pVAX-HGF characteristics, including morphology, particle size, zeta-potential, and DNA entrapment efficiency, were investigated. The pVAX-HGF nanocomposites with low toxicity and high transfection efficiency were screened by cell viability assay and cell transfection. The antifibrotic effect of pVAX-HGF nanocomposite on PF rats induced by bleomycin (BLM) was evaluated by pulmonary function measurement, pathological examination and collagen content assay.
Results: Different nanocomposites were prepared to deliver pVAX-HGF, in which mix1 (PEGPEI: PEI/pVAX-HGF) has lower potential and better entrapment ability.
Peg-pei: PEI/pVAX-HGF (N/P=25) nanocomposite with low toxicity and high transfection efficiency was administered to PF rats. After treatment with mix 1/pVAX-HGF, the index of lung function(including EF50, MV, TV, PEF and PIF) in mix 1/pVAX-HGF group was higher than that of the PF group. The number of cells in BALF of the mix 1/pVAX-HGF group was significantly lower than that of the PF groups, and the content of hydroxyproline(HYP) and collagen Type I (Col-I) in the lung of the mix 1/pVAX-HGF group was much lower than that of the PF groups in the early stage. The result of pathological examination showed that rats in the mix1/pVAX-HGF group showed obviously reduced alveolar septal thickening, fewer infiltrated inflammatory cells and less collagen deposition.
Conclusion: The PEG-PEI:PEI/pVAX-HGF nanocomposite can ameliorate PF induced by BLM. The pVAX-HGF nanocomposite is a latent therapeutic strategy for PF.
期刊介绍：
Current Drug Delivery aims to publish peer-reviewed articles, research articles, short and in-depth reviews, and drug clinical trials studies in the rapidly developing field of drug delivery. Modern drug research aims to build delivery properties of a drug at the design phase, however in many cases this idea cannot be met and the development of delivery systems becomes as important as the development of the drugs themselves.
The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance.
The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.
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