Hepatocyte Growth Factor Delivered by Nanocomposites for Gene Therapy of Bleomycin-Induced Pulmonary Fibrosis in Rats.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY Current drug delivery Pub Date : 2023-01-01 DOI:10.2174/1567201819666220613145417

Qi Guo, Yuxin Lu, Xiaochen Cheng, Fengjun Xiao, Qinglin Zhang, Peng Gao, Li Du

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Abstract

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.

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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。

背景:肺纤维化(PF)是一种慢性进行性间质性肺疾病。肝细胞生长因子(HGF)具有抗炎和抗纤维化作用，但由于半衰期短，潜力有限。方法:为了提高pVAX-HGF的转染效率，我们制备了装载编码HGF基因的质粒的聚乙烯亚胺聚乙二醇:聚乙烯亚胺/pVAX-HGF (PEG-PEI: PEI/pVAX-HGF)纳米复合材料。研究了PEG-PEI:PEI/pVAX-HGF的形态、粒径、ζ电位和DNA包埋效率等特性。通过细胞活力测定和细胞转染筛选了低毒性、高转染效率的pVAX-HGF纳米复合材料。采用肺功能测定、病理检查、胶原含量测定等方法观察pVAX-HGF纳米复合材料对博来霉素(BLM)致PF大鼠的抗纤维化作用。结果:制备了不同的纳米复合材料来递送pVAX-HGF，其中mix1 (PEGPEI: PEI/pVAX-HGF)具有较低的电位和较好的包载能力。Peg-pei: PEI/pVAX-HGF (N/P=25)纳米复合材料对PF大鼠进行低毒、高效转染。经mix 1/pVAX-HGF治疗后，mix 1/pVAX-HGF组肺功能指数(包括EF50、MV、TV、PEF、PIF)均高于PF组。混合1/pVAX-HGF组大鼠肺BALF细胞数量显著低于PF组，且混合1/pVAX-HGF组肺中羟基脯氨酸(HYP)和I型胶原(coli)含量在早期显著低于PF组。病理检查结果显示，mix1/pVAX-HGF组大鼠肺泡间隔增厚明显减轻，炎性细胞浸润减少，胶原沉积减少。结论:PEG-PEI:PEI/pVAX-HGF纳米复合材料可改善BLM诱导的PF。pVAX-HGF纳米复合材料是一种潜在的PF治疗策略。

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来源期刊

Current drug delivery PHARMACOLOGY & PHARMACY-

CiteScore

5.10

自引率

4.20%

发文量

170

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.