Bin Yu, Zheng Sun, Xuecheng Li, Aimei Qv, Muhammad Sohail, Yanli Li, Hui Xu, Ping Xiang
{"title":"Research Progress of Novel Drug Delivery Systems of Chinese Medicine Monomers based on Natural Silk Fibroin: A Mini-Review.","authors":"Bin Yu, Zheng Sun, Xuecheng Li, Aimei Qv, Muhammad Sohail, Yanli Li, Hui Xu, Ping Xiang","doi":"10.2174/1567201819666220413111439","DOIUrl":"https://doi.org/10.2174/1567201819666220413111439","url":null,"abstract":"<p><p>Traditional Chinese medicine (TCM) has a good curative effect, but its disadvantages include complex components, poor drug stability, potential drug interaction, etc. Therefore, it is particularly important to construct a novel drug delivery system that can load Chinese medicine monomers to solve this problem. Silk fibroin is a kind of natural polymer material with unique properties. It can be used as a carrier material to load Chinese medicine monomers to prepare novel drug delivery systems that significantly affect treating diseases without toxic and side effects. However, there is still a lack of a review on silk fibroin as a carrier material to load Chinese medicine monomers to explore and analyze the current research results and progress. Here, our article focuses on the in-depth excavation and analysis of the recent research on novel drug delivery systems prepared by silk fibroin and TCM monomers. Besides, the characteristics, existing problems, and prospects of silk fibroin are discussed and explained. It is hoped that this research can provide a reference and basis for the modernization of TCM, the design of novel drug delivery systems, the research and development of new drugs in the future, and contribute to the innovation of silk protein.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":"20 3","pages":"211-222"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10664770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chengshi Ding, Shumeng Li, Deya Wang, Zhongjing Tian, Meiling Kang, Yingxia Zhang, Jing Ma, Yanmei Deng, Kai Zhang
{"title":"Preparation of β-CD-Vitexin Microspheres and their Effects on SW480 Cell Proliferation.","authors":"Chengshi Ding, Shumeng Li, Deya Wang, Zhongjing Tian, Meiling Kang, Yingxia Zhang, Jing Ma, Yanmei Deng, Kai Zhang","doi":"10.2174/1567201819666220825090426","DOIUrl":"https://doi.org/10.2174/1567201819666220825090426","url":null,"abstract":"<p><strong>Objective: </strong>In order to overcome the insolution and low bioavailability of the vitexin in vivo, β-cyclodextrin-vitexin (β-CD-vitexin) microspheres were prepared, and their effects on the proliferation of SW480 cells were observed.</p><p><strong>Methods: </strong>Scanning electron microscopy, ultraviolet spectrum, Fourier transform infrared spectroscopy, and release rate analysis identified the formation of β-CD-vitexin microspheres. MTT assay detected the effect of β-CD-vitexin microspheres on tumor cell proliferation at 6, 12, 24, and 48 h. Fluorescence microscopy and flow cytometry were used to observe the effect of β-CD-vitexin microspheres on the apoptosis of SW480 cells. The mRNA expression of the p53 gene was measured by qPCR.</p><p><strong>Results: </strong>β-CD-vitexin microspheres were successfully prepared. SW480 cell proliferation was inhibited by 0.1, 0.2, and 0.4 mg/mL of β-CD-vitexin microspheres in a dose- and time-dependent manner, and the mechanism of proliferation inhibition was related to cell apoptosis caused by the upregulated expression of p53 gene.</p><p><strong>Conclusion: </strong>The preparation of β-CD-vitexin sustained release microspheres is feasible, and β-CDvitexin microspheres have potential anti-colorectal cancer value.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":"20 4","pages":"433-440"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9438789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Srividya Atmakuri, Shweta Nene, Dharmendra Khatri, Shashi Bala Singh, V R Sinha, Saurabh Srivastava
{"title":"Forging Ahead the Repositioning of Multitargeted Drug Ivermectin.","authors":"Srividya Atmakuri, Shweta Nene, Dharmendra Khatri, Shashi Bala Singh, V R Sinha, Saurabh Srivastava","doi":"10.2174/1567201819666220516163242","DOIUrl":"https://doi.org/10.2174/1567201819666220516163242","url":null,"abstract":"<p><p>With the advent of ivermectin, tremendous improvement in public health has been observed, especially in the treatment of onchocerciasis and lymphatic filariasis that created chaos mostly in rural, sub-Saharan Africa and Latin American countries. The discovery of ivermectin became a boon to millions of people that had suffered in the pandemic and still holds its pharmacological potential. Ivermectin continued to surprise scientists because of its notable role in the treatment of various other tropical diseases (Chagas, leishmaniasis, worm infections, etc.) and is viewed as the safest drug with the least toxic effects. The current review highlights its role in unexplored avenues towards forging ahead of the repositioning of this multitargeted drug in cancer, viral (the evaluation of the efficacy of ivermectin against SARS-Cov-2 is under investigation) and bacterial infection and malaria. This article also provides a glimpse of regulatory considerations of drug repurposing and current formulation strategies. Due to its broad-spectrum activity, multitargeted nature and promising efforts are put towards the repurposing of this drug throughout the field of medicine. This single drug originated from a microbe, changed the face of global health by proving its unmatched success and progressive efforts continue in maintaining its bequestnin the management of global health by decreasing the burden of various diseases worldwide.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":"20 8","pages":"1049-1066"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9463038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thu Thi Kim Ninh, Tuan Hiep Tran, Chi Ying F-Huang, Chien Ngoc Nguyen
{"title":"Application of Computational Screening Tools and Nanotechnology for Enhanced Drug Synergism in Cancer Therapy.","authors":"Thu Thi Kim Ninh, Tuan Hiep Tran, Chi Ying F-Huang, Chien Ngoc Nguyen","doi":"10.2174/1567201819666220426092538","DOIUrl":"https://doi.org/10.2174/1567201819666220426092538","url":null,"abstract":"<p><strong>Background: </strong>Chemoresistance continues to limit the recovery of patients with cancer. New strategies, such as combination therapy or nanotechnology, can be further improved.</p><p><strong>Objective: </strong>In this study, we applied the computational strategy by exploiting two databases (CellMiner and Prism) to sort out the cell lines sensitive to both anti-cancer drugs, paclitaxel (PTX) and dihydroartemisinin (DHA); both of which are potentially synergistic in several cell lines.</p><p><strong>Methods: </strong>The combination of PTX and DHA was screened at different ratios to select the optimal ratio that could inhibit lung adenocarcinoma NCI-H23 the most. To further enhance therapeutic efficacy, these combinations of drugs were incorporated into a nanosystem.</p><p><strong>Results: </strong>At a PTX:DHA ratio of 1:2 (w/w), the combined drugs obtained the best combination index (0.84), indicating a synergistic effect. The drug-loaded nanoparticles sized at 135 nm with the drug loading capacity of 15.5 ± 1.34 and 13.8 ± 0.56 corresponding to DHA and PTX, respectively, were used. The nano-sized particles improved drug internalization into the cells, resulting in the significant inhibition of cell growth at all tested concentrations (p < 0.001). Additionally, α-tubulin aggregation, DNA damage suggested the molecular mechanism behind cell death upon PTX-DHA-loaded nanoparticle treatment. Moreover, the rate of apoptosis increased from approximately 5% to more than 20%, and the expression of apoptotic proteins changed 4 and 3 folds corresponding to p-53 and Bcl-2, respectively.</p><p><strong>Conclusion: </strong>This study was designed thoroughly by screening cell lines for the optimization of formulations. This novel approach could pave the way for the selection of combined drugs for precise cancer treatment.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":"20 7","pages":"1015-1029"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulatory Aspects, Types and Bioapplications of Metallic Nanoparticles: A Review.","authors":"Shrutee Pawar, Anjali Takke","doi":"10.2174/1567201819666220817110025","DOIUrl":"https://doi.org/10.2174/1567201819666220817110025","url":null,"abstract":"<p><strong>Background: </strong>Nanotechnology is rapidly advancing in almost every area, such as the pharmaceutical industry, food industry, nano fabrics, electronics, wastewater treatment, and agriculture.</p><p><strong>Introduction: </strong>Metallic nanoparticles are commonly used in various fields but are especially important in the pharmaceutical industry. Metallic nanoparticles have a size range of 10 nm to 100 nm.</p><p><strong>Methods: </strong>Two techniques are used to synthesize metallic nanoparticles, the top-down approach and the bottom-up approach. These techniques can be synthesized using three different methods: physical, chemical, and biological. Chemical methods include coprecipitation, reduction, sonochemical, solvothermal, and others, while physical methods include discharge, milling, and ion implantation. Biological methods include plants and their extracts, agricultural wastes, microorganisms, and seaweeds. Scanning electron microscopy, transmission electron microscopy, dynamic light scanning, and other techniques are used to characterize them.</p><p><strong>Results: </strong>All metallic nanoparticles are biocompatible and have special optical, electrical, magnetic, and chemical properties. They are used in various industries, including the pharmaceutical industry as an anticancer agent, antibacterial, antifungal, antioxidant, antidiabetic, and biosensors. Gold, silver, iron oxide, zinc oxide, platinum, copper oxide, and palladium nanoparticles are the most common metal nanoparticles used in the pharmaceutical industry. Monometallic and multimetallic nanoparticles are broadly classified under this.</p><p><strong>Conclusion: </strong>This article focuses on the major metallic nanoparticle groups, including synthesis, applications, case studies, toxicity, regulatory aspects and innovative approaches to metallic nanomaterials.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":"20 7","pages":"857-883"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arshad Ali Khan, Safia Akhtar, Yogesh Yadav, Atiya Akhtar, Walla Alelwani, Azzah M Bannunah, Syed Mahmood
{"title":"Lopinavir-Loaded Self-Nanoemulsifying Drug Delivery System for Enhanced Solubility: Development, Characterisation and Caco-2 Cell Uptake.","authors":"Arshad Ali Khan, Safia Akhtar, Yogesh Yadav, Atiya Akhtar, Walla Alelwani, Azzah M Bannunah, Syed Mahmood","doi":"10.2174/1567201819666220817111054","DOIUrl":"https://doi.org/10.2174/1567201819666220817111054","url":null,"abstract":"<p><strong>Background: </strong>The antiretroviral protease inhibitor drug, lopinavir (LPV), is used to treat HIV-1 infection. LPV is known to have limited oral bioavailability, which may be attributed to its poor aqueous solubility, low efficacy and high first-pass metabolism. Self-nanoemulsifying drug delivery systems (SNEDDS) for LPV have been developed and optimised to counter the current issues.</p><p><strong>Methods: </strong>The titration method was used to prepare LPV-loaded SNEDDS (LPV-SNEDDS). Six different pseudo-ternary phase diagrams were constructed to identify the nanoemulsifying region. The developed formulations were chosen in terms of globule size < 100 nm, dispersity ≤ 0.5, dispersibility (Grade A) and% transmittance > 85. Heating-cooling cycle, freeze-thaw cycle, and centrifugation studies were performed to confirm the stability of the developed SNEDDS.</p><p><strong>Results: </strong>The final LPV-SNEDDS (L-14) droplet size was 58.18 ± 0.62 nm, with polydispersity index, zeta potential, and entrapment efficiency (EE%) values of 0.326 ± 0.005, -22.08 ± 1.2 mV, and 98.93 ± 1.18%, respectively. According to high-resolution transmission electron microscopy (HRTEM) analysis, the droplets in the optimised formulation were < 60 nm in size. The selected SNEDDS released nearly 99% of the LPV within 30 min, which was significantly (p < 0.05) higher than the LPV-suspension in methylcellulose (0.5% w/v). It indicates the potential use of SNEDDS to enhance the solubility of LPV, which eventually could help improve the oral bioavailability of LPV. The Caco-2 cellular uptake study showed a significantly (p < 0.05) higher LPV uptake from the SNEEDS (LPV-SNEDDS-L-14) than the free LPV (LPV-suspension).</p><p><strong>Conclusion: </strong>The LPV-SNEDDS could be a potential carrier for LPV oral delivery.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":"20 10","pages":"1474-1486"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9497084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shikha Mahant, Abhishek Kumar Sharma, Himanshu Gandhi, Ridhima Wadhwa, Kamal Dua, Deepak N Kapoor
{"title":"Emerging Trends and Potential Prospects in Vaginal Drug Delivery.","authors":"Shikha Mahant, Abhishek Kumar Sharma, Himanshu Gandhi, Ridhima Wadhwa, Kamal Dua, Deepak N Kapoor","doi":"10.2174/1567201819666220413131243","DOIUrl":"https://doi.org/10.2174/1567201819666220413131243","url":null,"abstract":"<p><p>The vagina is an essential part of the female reproductive system and offers many potential benefits over conventional drug delivery, including a large surface area for drug absorption, relatively low enzymatic activity, avoiding first-pass effects, and ease of administration. The vaginal mucosal cavity is an effective route for administering therapeutic agents that are intended both for local and systemic administration. The present review provides a comprehensive overview of recent trends and developments in vaginal drug delivery. Marketed formulations and products under clinical study are also reviewed. Various novel vaginal delivery systems have been studied in recent years as effective tools for delivering a range of therapeutic agents to the vagina. These systems offer numerous benefits, including sustained delivery, improved bioavailability, effective permeation, and higher efficacy. The recent focus of the scientific community is on the development of safe and efficient drug delivery systems, such as nanoparticles, microparticles, vesicular systems, vaginal rings, microneedles, etc., for vaginal application. Various factors, such as the physicochemical properties of the drugs, the volume and composition of the vaginal fluid, the pH of the vaginal fluid, the thickness of the vaginal epithelium, and the influence of sexual intercourse may influence the release of drugs from the delivery system and subsequent absorption from the vaginal route. To date, only a limited number of in vivo studies on novel vaginal DDS have been reported. Additionally, drug release kinetics under varying vaginal environments is also not well understood. More research is needed to ensure the suitability, biocompatibility, and therapeutic effectiveness of novel DDS for vaginal delivery. Although numerous strategies and interventions have been developed, clinical translation of these systems remains a challenge. The toxicity of the carrier system is also an important consideration for future clinical applications.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":"20 6","pages":"730-751"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9540103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Celebrating a Century of Insulin Discovery: A Critical Appraisal of the Emerging Alternative Insulin Delivery Systems.","authors":"Ntethelelo Sibiya, Bonisiwe Mbatha, Phikelelani Ngubane, Andile Khathi","doi":"10.2174/1567201819666220531101203","DOIUrl":"https://doi.org/10.2174/1567201819666220531101203","url":null,"abstract":"<p><p>Since the discovery of insulin, continuous developments of this peptide have led to better management of diabetes mellitus, thus leading to a decrease in diabetes-related mortality. Despite these developments, we have seen an increase in diabetes cases, which has further necessitated more innovative methods for diabetes management. The subcutaneous administration of insulin remains the mainstay therapy for type 1 diabetes mellitus. However, despite the availability of insulin analogues with improved pharmacokinetics, challenges with conventional administration exist. The challenges associated with insulin injections include hypoglycaemic episodes, needle phobia, and injection-site inflammation, which all have been reported to reduce patient compliance. Ongoing research on diabetes management strives to develop therapies that provide improved glycaemic control with minimal side effects. In part, for these reasons, we have seen an increase in the search and development of alternative insulin delivery systems that are envisaged to circumvent the shortfalls associated with the conventional administration route. Several alternative drug delivery systems, such as oral, pulmonary, buccal, nasal, and transdermal, have been explored in the last century. These efforts have not been without victory, as we have seen the emergence of pulmonary (Exubera and Afrezza) and buccal insulin delivery systems licenced for therapeutic use. Despite the success seen in these two systems, their marketability and popularity have been severely compromised due to reported safety concerns. Although oral insulin delivery has always shown promise in the past decades; however, it was only limited to preclinical trials. The main challenge associated with this delivery route is poor bioavailability, which necessitates high insulin concentration to be administered. Due to recent developments, oral insulin has reached phase 3 clinical trials. It is believed that patients would prefer oral insulin as their preference is often observed for oral antidiabetics over injected ones. In the last decade, transdermal insulin has also gained interest, where delivery of insulin with a concomitant reduction in blood glucose concentration has been demonstrated in vivo. However, at present, there are no clinical studies that have reported the efficacy of transdermal insulin administration. With technological advancement, there is a potential to develop yet another insulin delivery system that would likely enter the markets. As these novel delivery systems have been found to be effective, emerging competing products should be welcome and appreciated.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":"20 6","pages":"656-668"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Designing, Structural Determination, and Antibacterial Activity of Injectable Ciprofloxacin-loaded gelatin-sodium Carboxymethyl Cellulose composite Nanogels against <i>Staphylococcus aureus</i>.","authors":"Jinhuan Liu, Wei Song, Samah Attia Algharib, Wanhe Luo, Wei Chen","doi":"10.2174/1567201819666220513121219","DOIUrl":"https://doi.org/10.2174/1567201819666220513121219","url":null,"abstract":"<p><strong>Background: </strong>The development of nanogels has become an attractive strategy to enhance the antibacterial activity performance of bacteria.</p><p><strong>Methods: </strong>The ciprofloxacin composite nanogels were successfully prepared by electrostatic interaction between gelatin (positive charge) and CMC (negative charge) with the help of sodium tripolyphosphate (TPP) as ionic crosslinkers, to increase the antibacterial activity of ciprofloxacin against Staphylococcus aureus (S. aureus) mastitis infection. The formulation screening, characterization, in vitro release, antibacterial activity, and biosafety were studied.</p><p><strong>Results: </strong>The optimized formulation was fabricated of 20 mg/mL (CMC) and 50mg/mL (gelatin). The optimized ciprofloxacin composite nanogels were homogenous canary yellow suspension with a sedimentation rate of 1 and were incorporated in nano-sized cross-linked polymeric networks. The particle sizes were distributed as, 402.7±1.3 nm, PDI of 0.12±0.01, ZP of -24.5±0.2mv, EE of 74.28%±0.03%, LC of 20.5%±0.05%. Scanning electron microscope images revealed that ciprofloxacin might be incorporated in nano-sized cross-linked polymeric networks. Fourier transform infrared showed that the spontaneous electrostatic interactions between CMC and gelatin produce the network structure and form the composite nanogels. Meanwhile, in vitro release study showed that ciprofloxacin composite nanogels had sustained-release performances. The ciprofloxacin composite nanogels had shown better antibacterial activity against SCV 102 isolate than S. aureus ATCC 29213 and S. aureus 101isolates. The biosafety studies suggested the great promise of the injectable ciprofloxacin composite nanogels as a biocompatible breast injection.</p><p><strong>Conclusion: </strong>This study will afford a potential approach for developing injectable ciprofloxacin-loaded gelatin-CMC composite nanogels for cow S. aureus mastitis therapy.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":"20 9","pages":"1327-1336"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9548771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qi Guo, Yuxin Lu, Xiaochen Cheng, Fengjun Xiao, Qinglin Zhang, Peng Gao, Li Du
{"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":"https://doi.org/10.2174/1567201819666220613145417","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":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9549511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}