Pub Date : 2024-03-01Epub Date: 2023-05-12DOI: 10.1080/08982104.2023.2209642
Sharayu Govardhane, Pravin Shende
Phthalocyanine is a blue-colored macrocyclic compound with excellent anti-oxidant and lipid-peroxidation abilities due to its intermolecular π-π stacking structure. Antioxidants inhibit intracellular reactive oxygen species formation and decrease oxidation defense ability of the enzymes in diabetes management. The present study aimed to fabricate concanavalin A conjugated phthalocyanine-loaded cochleates (Formulation PhConA) as a glucose-sensitive lipidic system and estimate its efficacy in streptozotocin-induced male Sprague Dawley diabetic rats for 28 days. Thin-film hydration and trapping methods were used in the preparation of liposomes and cochleates, respectively, whereas the surface was modified for concanavalin A conjugation using EDAC: NHS (1:1). Formulation PhConA with rod-shaped structures showed particle size of 415.7 ± 0.46 nm, PdI value of 0.435 ± 0.09, encapsulation efficiency of 85.64 ± 0.34%, and 84.55 ± 0.29% release of phthalocyanine for 56 h. The circular dichroism study displayed a slight deviation after the conjugation effect of concanavalin A to cochleates. The in-vivo studies of the formulation PhConA improved the blood glucose levels along with defensive effect on the liver to overcome the hyperlipidemic effect. The rigid structure of cochleates prolongs the drug elimination from systemic circulation and extends its effect for a longer duration by decreasing the blood glucose level. Thus, the glucose-sensitive formulation PhConA showed significant improvement in diabetic rats within the period of 28 days by improving the oxidative defense and protecting the pancreatic β-cells.
{"title":"Phthalocyanine-based glucose-responsive nanocochleates for dynamic prevention of β-cell damage in diabetes.","authors":"Sharayu Govardhane, Pravin Shende","doi":"10.1080/08982104.2023.2209642","DOIUrl":"10.1080/08982104.2023.2209642","url":null,"abstract":"<p><p>Phthalocyanine is a blue-colored macrocyclic compound with excellent anti-oxidant and lipid-peroxidation abilities due to its intermolecular π-π stacking structure. Antioxidants inhibit intracellular reactive oxygen species formation and decrease oxidation defense ability of the enzymes in diabetes management. The present study aimed to fabricate concanavalin A conjugated phthalocyanine-loaded cochleates (Formulation PhConA) as a glucose-sensitive lipidic system and estimate its efficacy in streptozotocin-induced male Sprague Dawley diabetic rats for 28 days. Thin-film hydration and trapping methods were used in the preparation of liposomes and cochleates, respectively, whereas the surface was modified for concanavalin A conjugation using EDAC: NHS (1:1). Formulation PhConA with rod-shaped structures showed particle size of 415.7 ± 0.46 nm, PdI value of 0.435 ± 0.09, encapsulation efficiency of 85.64 ± 0.34%, and 84.55 ± 0.29% release of phthalocyanine for 56 h. The circular dichroism study displayed a slight deviation after the conjugation effect of concanavalin A to cochleates. The <i>in-vivo</i> studies of the formulation PhConA improved the blood glucose levels along with defensive effect on the liver to overcome the hyperlipidemic effect. The rigid structure of cochleates prolongs the drug elimination from systemic circulation and extends its effect for a longer duration by decreasing the blood glucose level. Thus, the glucose-sensitive formulation PhConA showed significant improvement in diabetic rats within the period of 28 days by improving the oxidative defense and protecting the pancreatic β-cells.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"44-59"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9452465","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}
Pub Date : 2023-12-13DOI: 10.1080/08982104.2023.2293844
Lei Yang, Nuan Liu, Yang Yang
This study focused on investigating the mechanism of the astragaloside IV-induced bone marrow mesenchymal stem cell exosome (AS-IV-MSC-exo)/microRNA(miR)-411/HIF-1α axis in affecting vascular neova...
{"title":"Astragaloside IV-induced BMSC exosomes promote neovascularization and protect cardiac function in myocardial infarction mice via the miR-411/HIF-1α axis","authors":"Lei Yang, Nuan Liu, Yang Yang","doi":"10.1080/08982104.2023.2293844","DOIUrl":"https://doi.org/10.1080/08982104.2023.2293844","url":null,"abstract":"This study focused on investigating the mechanism of the astragaloside IV-induced bone marrow mesenchymal stem cell exosome (AS-IV-MSC-exo)/microRNA(miR)-411/HIF-1α axis in affecting vascular neova...","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":"180 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138680041","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}
Pub Date : 2023-12-01Epub Date: 2023-03-28DOI: 10.1080/08982104.2023.2191718
Yajing Wang, Ziwei Ding, Shiqun Lv, Jie Liu, Jie Pan, Yingcong Yu, Jun Gao, Xianfeng Huang
tLyP-1 peptide is verified to recognize neuropilin (NRP) receptors overexpressed on the surface of both glioma cells and endothelial cells of angiogenic blood vessels. In the present study, tLyP-1 was conjugated with DSPE-PEG2000 to prepare tLyP-1-DSPE-PEG2000, which was further employed to prepare tLyP-1 functionalized nanoliposome (tLyP-1-Lip) to achieve enhancing target of glioblastoma. Process parameters were systematically studied to investigate the feasibility of tuning the internal water phase of nanoliposomes and encapsulating more Temozolomide (TMZ). The particle size, Zeta potential, and encapsulation efficiency of tLyP-1-Lip/TMZ were fully characterized in comparison with conventional nanoliposomes (Lip-TMZ) and PEGylated nanoliposomes (PEG-Lip/TMZ). The release behaviors of TMZ from PEG-Lip/TMZ and tLyP-1-Lip/TMZ are similar and slower than TMZ-Lip in acidic solutions. The tLyP-1-Lip/TMZ demonstrated the strongest cytotoxicity in comparison with TMZ-Lip and PEG-Lip/TMZ in both U87 and HT22 cells, and displayed the highest cellular internalization. The pharmacokinetic studies in rats revealed that tLyP-1-Lip/TMZ showed a 1.4-fold (p<0.001) increase in AUCINF_obs and a 1.4-fold decrease (p<0.01) in clearance compared with PEG-Lip/TMZ. We finally confirmed by in vivo imaging that tLyP-1-Lip were able to penetrate the brains and tumors of mice.
{"title":"Development of tLyP-1 functionalized nanoliposomes with tunable internal water phase for glioma targeting.","authors":"Yajing Wang, Ziwei Ding, Shiqun Lv, Jie Liu, Jie Pan, Yingcong Yu, Jun Gao, Xianfeng Huang","doi":"10.1080/08982104.2023.2191718","DOIUrl":"10.1080/08982104.2023.2191718","url":null,"abstract":"<p><p>tLyP-1 peptide is verified to recognize neuropilin (NRP) receptors overexpressed on the surface of both glioma cells and endothelial cells of angiogenic blood vessels. In the present study, tLyP-1 was conjugated with DSPE-PEG2000 to prepare tLyP-1-DSPE-PEG2000, which was further employed to prepare tLyP-1 functionalized nanoliposome (tLyP-1-Lip) to achieve enhancing target of glioblastoma. Process parameters were systematically studied to investigate the feasibility of tuning the internal water phase of nanoliposomes and encapsulating more Temozolomide (TMZ). The particle size, Zeta potential, and encapsulation efficiency of tLyP-1-Lip/TMZ were fully characterized in comparison with conventional nanoliposomes (Lip-TMZ) and PEGylated nanoliposomes (PEG-Lip/TMZ). The release behaviors of TMZ from PEG-Lip/TMZ and tLyP-1-Lip/TMZ are similar and slower than TMZ-Lip in acidic solutions. The tLyP-1-Lip/TMZ demonstrated the strongest cytotoxicity in comparison with TMZ-Lip and PEG-Lip/TMZ in both U87 and HT22 cells, and displayed the highest cellular internalization. The pharmacokinetic studies in rats revealed that tLyP-1-Lip/TMZ showed a 1.4-fold (<i>p</i><b> </b><<b> </b>0.001) increase in AUC<sub>INF_obs</sub> and a 1.4-fold decrease (<i>p</i><b> </b><<b> </b>0.01) in clearance compared with PEG-Lip/TMZ. We finally confirmed by <i>in vivo</i> imaging that tLyP-1-Lip were able to penetrate the brains and tumors of mice.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"353-367"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9193097","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}
The main challenge of using nanoliposome systems is controlling their size and stability. In order to overcome this challenge, according to the research conducted at the Research Centre for New Technologies of Biological Engineering, University of Tehran, a model for predicting the size and stability of nanoliposome systems based on thermodynamic relations has been presented. In this model, by using the presented equations and without performing many experiments in the laboratory environment, the effect of temperature, ionic power and different pH can be considered simultaneously whereas examining the components of size, stability and any feature were considered before. Synthesis and application of liposomal nanocarriers in different operating conditions can be investigated and predicted, and due to the change in temperature and pH, the smallest size of th system can be obtained. In this study, we were able to model the synthesis and storage conditions of liposomal nanocarriers at different temperatures and acidic, neutral and alkaline pHs, based on the calculation of mathematical equations. This model also indicates that with increasing temperature, the radius increases but with increasing pH, the radius first increases and then decreases. Therefore, this model can be used to predict size and stability in different operating conditions. In fact, with this modelling method, there is no need to study through laboratory methods and analysis to determine the size, stability and surface loads, and in terms of Accuracy, time and cost savings are affordable.
{"title":"Prognosticating the effect of temperature and pH parameters on size and stability of the nanoliposome system based on thermodynamic modeling.","authors":"Fardin Rahimi, Pari Hajizadeh, Ghassem Amoabediny, Bahman Ebrahimi, Mansoor Khaledi, Fatemeh Sameni, Hamed Afkhami, Shahriar Bakhti, Elham Rafiee Taqanaki, Mahdi Zafari","doi":"10.1080/08982104.2023.2203250","DOIUrl":"10.1080/08982104.2023.2203250","url":null,"abstract":"<p><p>The main challenge of using nanoliposome systems is controlling their size and stability. In order to overcome this challenge, according to the research conducted at the Research Centre for New Technologies of Biological Engineering, University of Tehran, a model for predicting the size and stability of nanoliposome systems based on thermodynamic relations has been presented. In this model, by using the presented equations and without performing many experiments in the laboratory environment, the effect of temperature, ionic power and different pH can be considered simultaneously whereas examining the components of size, stability and any feature were considered before. Synthesis and application of liposomal nanocarriers in different operating conditions can be investigated and predicted, and due to the change in temperature and pH, the smallest size of th system can be obtained. In this study, we were able to model the synthesis and storage conditions of liposomal nanocarriers at different temperatures and acidic, neutral and alkaline pHs, based on the calculation of mathematical equations. This model also indicates that with increasing temperature, the radius increases but with increasing pH, the radius first increases and then decreases. Therefore, this model can be used to predict size and stability in different operating conditions. In fact, with this modelling method, there is no need to study through laboratory methods and analysis to determine the size, stability and surface loads, and in terms of Accuracy, time and cost savings are affordable.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"392-409"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9452464","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}
Pub Date : 2023-12-01Epub Date: 2023-03-15DOI: 10.1080/08982104.2023.2187821
Yutong He, Mees Barlag, Josée A Plantinga, Grietje Molema, Jan A A M Kamps
Increased understanding of chronic inflammatory diseases and the role of endothelial cell (EC) activation herein, have urged interest in sophisticated strategies to therapeutically intervene in activated EC to treat these diseases. Liposome-mediated delivery of therapeutic siRNA in inflammation-activated EC is such a strategy. In this study, we describe the design and characterisation of two liposomal siRNA delivery systems formulated with the cationic MC3 lipid or MC3/SAINT mixed lipids, referred to as MC3-O-Somes (MOS) and MC3/SAINT-O-Somes (MSS). The two formulations showed comparable physicochemical properties, except for better siRNA encapsulation efficiency in the MSS formulation. Antibody-mediated VCAM-1 targeting (AbVCAM-1) increased the association of the targeted MOS and MSS with activated EC, although the targeted MOS showed a significantly higher VCAM-1 specific association than the targeted MSS. AbVCAM-1 MSS containing RelA siRNA achieved significant downregulation of RelA expression, while AbVCAM-1 MOS containing RelA siRNA did not downregulate RelA expression in activated EC. Additionally, AbVCAM-1 MSS containing RelA siRNA showed low cytotoxicity in EC and at the same time prohibited endothelial inflammatory activation by reducing expression of cell adhesion molecules. The AbVCAM-1 MSS formulation is a novel siRNA delivery system based on a combination of the cationic lipids MC3 and SAINT, that shows good physicochemical characteristics, enhanced endothelial cell association, improved transfection activity, low toxicity and significant anti-inflammatory effect, thereby complying with the requirements for future in vivo investigations.
随着对慢性炎症性疾病和内皮细胞(EC)激活作用的了解的增加,人们对复杂的策略产生了兴趣,以治疗干预活化的EC来治疗这些疾病。脂质体介导的治疗性siRNA在炎症激活的EC中传递就是这样一种策略。在这项研究中,我们描述了两种由阳离子MC3脂质或MC3/SAINT混合脂质配制的脂质体siRNA递送系统的设计和表征,称为MC3- o - some (MOS)和MC3/SAINT- o - some (MSS)。两种制剂的理化性质相当,但MSS制剂的siRNA包封效率更高。抗体介导的VCAM-1靶向(AbVCAM-1)增加了靶向MOS和MSS与活化EC的关联,尽管靶向MOS显示出明显高于靶向MSS的VCAM-1特异性关联。含有RelA siRNA的AbVCAM-1 MSS显著下调了RelA的表达,而含有RelA siRNA的AbVCAM-1 MOS在活化EC中不下调RelA的表达。此外,含有RelA siRNA的AbVCAM-1 MSS在EC中表现出较低的细胞毒性,同时通过减少细胞粘附分子的表达来抑制内皮细胞的炎症激活。AbVCAM-1 MSS制剂是一种基于阳离子脂质MC3和SAINT结合的新型siRNA递送系统,具有良好的理化特性,增强内皮细胞的关联性,提高转染活性,低毒性和显著的抗炎作用,符合未来体内研究的要求。
{"title":"MC3/SAINT-O-Somes, a novel liposomal delivery system for efficient and safe delivery of siRNA into endothelial cells.","authors":"Yutong He, Mees Barlag, Josée A Plantinga, Grietje Molema, Jan A A M Kamps","doi":"10.1080/08982104.2023.2187821","DOIUrl":"10.1080/08982104.2023.2187821","url":null,"abstract":"<p><p>Increased understanding of chronic inflammatory diseases and the role of endothelial cell (EC) activation herein, have urged interest in sophisticated strategies to therapeutically intervene in activated EC to treat these diseases. Liposome-mediated delivery of therapeutic siRNA in inflammation-activated EC is such a strategy. In this study, we describe the design and characterisation of two liposomal siRNA delivery systems formulated with the cationic MC3 lipid or MC3/SAINT mixed lipids, referred to as MC3-O-Somes (MOS) and MC3/SAINT-O-Somes (MSS). The two formulations showed comparable physicochemical properties, except for better siRNA encapsulation efficiency in the MSS formulation. Antibody-mediated VCAM-1 targeting (Ab<sub>VCAM-1</sub>) increased the association of the targeted MOS and MSS with activated EC, although the targeted MOS showed a significantly higher VCAM-1 specific association than the targeted MSS. Ab<sub>VCAM-1</sub> MSS containing RelA siRNA achieved significant downregulation of RelA expression, while Ab<sub>VCAM-1</sub> MOS containing RelA siRNA did not downregulate RelA expression in activated EC. Additionally, Ab<sub>VCAM-1</sub> MSS containing RelA siRNA showed low cytotoxicity in EC and at the same time prohibited endothelial inflammatory activation by reducing expression of cell adhesion molecules. The Ab<sub>VCAM-1</sub> MSS formulation is a novel siRNA delivery system based on a combination of the cationic lipids MC3 and SAINT, that shows good physicochemical characteristics, enhanced endothelial cell association, improved transfection activity, low toxicity and significant anti-inflammatory effect, thereby complying with the requirements for future in vivo investigations.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"328-337"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9114679","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}
Pub Date : 2023-12-01Epub Date: 2023-04-19DOI: 10.1080/08982104.2023.2199068
S Swathi Krishna, M S Sudheesh, Vidya Viswanad
High local delivery of anti-infectives to the lungs is required for activity against infections of the lungs. The present pandemic has highlighted the potential of pulmonary delivery of anti-infective agents as a viable option for infections like Covid-19, which specifically causes lung infections and mortality. To prevent infections of such type and scale in the future, target-specific delivery of drugs to the pulmonary region is a high-priority area in the field of drug delivery. The suboptimal effect of oral delivery of anti-infective drugs to the lungs due to the poor biopharmaceutical property of the drugs makes this delivery route very promising for respiratory infections. Liposomes have been used as an effective delivery system for drugs due to their biocompatible and biodegradable nature, which can be used effectively for target-specific drug delivery to the lungs. In the present review, we focus on the use of liposomal drug delivery of anti-infectives for the acute management of respiratory infections in the wake of Covid-19 infection.
{"title":"Liposomal drug delivery to the lungs: a post covid-19 scenario.","authors":"S Swathi Krishna, M S Sudheesh, Vidya Viswanad","doi":"10.1080/08982104.2023.2199068","DOIUrl":"10.1080/08982104.2023.2199068","url":null,"abstract":"<p><p>High local delivery of anti-infectives to the lungs is required for activity against infections of the lungs. The present pandemic has highlighted the potential of pulmonary delivery of anti-infective agents as a viable option for infections like Covid-19, which specifically causes lung infections and mortality. To prevent infections of such type and scale in the future, target-specific delivery of drugs to the pulmonary region is a high-priority area in the field of drug delivery. The suboptimal effect of oral delivery of anti-infective drugs to the lungs due to the poor biopharmaceutical property of the drugs makes this delivery route very promising for respiratory infections. Liposomes have been used as an effective delivery system for drugs due to their biocompatible and biodegradable nature, which can be used effectively for target-specific drug delivery to the lungs. In the present review, we focus on the use of liposomal drug delivery of anti-infectives for the acute management of respiratory infections in the wake of Covid-19 infection.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"410-424"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9420297","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}
Pub Date : 2023-12-01Epub Date: 2023-04-05DOI: 10.1080/08982104.2023.2193845
Fengmei Li, Yan Wang, Wenqun Li, Junyong Wu, Shengnan Li, Xiongbin Hu, Tiantian Tang, Xinyi Liu
Based on the inhibition of mitochondrial permeability transition pore (mPTP) opening, puerarin (PUE) has a good potential to reduce myocardial ischemia/reperfusion injury (MI/RI). However, the lack of targeting of free PUE makes it difficult to reach the mitochondria. In this paper, we constructed matrix metalloproteinase-targeting peptide (MMP-TP) and triphenylphosphonium (TPP) cation co-modified liposomes loaded with PUE (PUE@T/M-L) for mitochondria-targeted drug delivery. PUE@T/M-L had a favorable particle size of 144.9 ± 0.8 nm, an encapsulation efficiency of 78.9 ± 0.6%, and a sustained-release behavior. The results of cytofluorimetric experiments showed that MMP-TP and TPP double-modified liposomes (T/M-L) enhanced intracellular uptake, escaped lysosomal capture, and promoted drug targeting into mitochondria. In addition, PUE@T/M-L enhanced the viability of hypoxia-reoxygenation (H/R) injured H9c2 cells by inhibiting mPTP opening and reactive oxygen species (ROS) production, reducing Bax expression and increasing Bcl-2 expression. It was inferred that PUE@T/M-L delivered PUE into the mitochondria of H/R injured H9c2 cells, resulting in a significant increase in cellular potency. Based on the ability of MMP-TP to bind the elevated expression of matrix metalloproteinases (MMPs), T/M-L had excellent tropism for Lipopolysaccharide (LPS) -stimulated macrophages and can significantly reduce TNF-α and ROS levels, thus allowing both drug accumulation in ischemic cardiomyocytes and reducing inflammatory stimulation during MI/RI. Fluorescence imaging results of the targeting effect using a DiR probe also indicated that DiR@T/M-L could accumulate and retain in the ischemic myocardium. Taken together, these results demonstrated the promising application of PUE@T/M-L for mitochondria-targeted drug delivery to achieve maximum therapeutic efficacy of PUE.
{"title":"Enhanced protection against hypoxia/reoxygenation-induced apoptosis in H9c2 cells by puerarin-loaded liposomes modified with matrix metalloproteinases-targeting peptide and triphenylphosphonium.","authors":"Fengmei Li, Yan Wang, Wenqun Li, Junyong Wu, Shengnan Li, Xiongbin Hu, Tiantian Tang, Xinyi Liu","doi":"10.1080/08982104.2023.2193845","DOIUrl":"10.1080/08982104.2023.2193845","url":null,"abstract":"<p><p>Based on the inhibition of mitochondrial permeability transition pore (mPTP) opening, puerarin (PUE) has a good potential to reduce myocardial ischemia/reperfusion injury (MI/RI). However, the lack of targeting of free PUE makes it difficult to reach the mitochondria. In this paper, we constructed matrix metalloproteinase-targeting peptide (MMP-TP) and triphenylphosphonium (TPP) cation co-modified liposomes loaded with PUE (PUE@T/M-L) for mitochondria-targeted drug delivery. PUE@T/M-L had a favorable particle size of 144.9 ± 0.8 nm, an encapsulation efficiency of 78.9 ± 0.6%, and a sustained-release behavior. The results of cytofluorimetric experiments showed that MMP-TP and TPP double-modified liposomes (T/M-L) enhanced intracellular uptake, escaped lysosomal capture, and promoted drug targeting into mitochondria. In addition, PUE@T/M-L enhanced the viability of hypoxia-reoxygenation (H/R) injured H9c2 cells by inhibiting mPTP opening and reactive oxygen species (ROS) production, reducing Bax expression and increasing Bcl-2 expression. It was inferred that PUE@T/M-L delivered PUE into the mitochondria of H/R injured H9c2 cells, resulting in a significant increase in cellular potency. Based on the ability of MMP-TP to bind the elevated expression of matrix metalloproteinases (MMPs), T/M-L had excellent tropism for Lipopolysaccharide (LPS) -stimulated macrophages and can significantly reduce TNF-α and ROS levels, thus allowing both drug accumulation in ischemic cardiomyocytes and reducing inflammatory stimulation during MI/RI. Fluorescence imaging results of the targeting effect using a DiR probe also indicated that DiR@T/M-L could accumulate and retain in the ischemic myocardium. Taken together, these results demonstrated the promising application of PUE@T/M-L for mitochondria-targeted drug delivery to achieve maximum therapeutic efficacy of PUE.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"378-391"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9241762","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}
In this study, N'-(3-aminopropyl)-N-(3'-(carbamoyl cholesteryl) propyl)-glycine amide (A) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE, D) (AD) liposomes were synthesised at molar ratios of 50:25 (AD5025), 50:50 (AD5050) and 50:75 (AD5075) and complexed with plasmid, pTRAIL-EGFP. AD liposome/pTRAIL-EGFP were evaluated for their complex ability, particle size, polydispersity index, zeta potential, expression of pTRAIL-EGFP, cytotoxicity, cell growth inhibition and apoptosis induction in KB cells. AD liposomes complexed completely with pTRAIL-EGFP at AD liposome/DNA ratios of above 4.5/1. The particle size of AD liposome/pTRAIL-EGFP ranged from 180 ± 8 to 1,072 ± 657 nm depending on the proportion of lipid composition and liposome/DNA ratio. The extent of gene expression of pTRAIL-EGFP via AD liposome/pTRAIL-EGFP was significantly higher than that of the cells treated with pTRAIL-EGFP and depended on the AD liposome/DNA ratio. Cytotoxicity of AD liposomes was dependent on A and D molar ratio. Cell growth inhibition of AD liposome/pTRAIL-EGFP was significantly higher than that of the cells treated with pTRAIL-EGFP. The amount of late apoptotic and dead cells of AD liposome/pTRAIL-EGFP was significantly higher than that of cells treated with pTRAIL-EGFP. From this study that one can conclude that AD liposomes can carry and deliver pTRAIL-EGFP into KB cells resulting in cell growth inhibition and cell death.
{"title":"N'-(3-Aminopropyl)-N-(3'-(carbamoyl cholesteryl) propyl)-glycine amide liposomes for delivery of pTRAIL-EGFP.","authors":"Wanlop Weecharangsan, Nuttapon Apiratikul, Jantana Yahuafai","doi":"10.1080/08982104.2023.2193638","DOIUrl":"10.1080/08982104.2023.2193638","url":null,"abstract":"<p><p>In this study, N'-(3-aminopropyl)-N-(3'-(carbamoyl cholesteryl) propyl)-glycine amide (A) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE, D) (AD) liposomes were synthesised at molar ratios of 50:25 (AD5025), 50:50 (AD5050) and 50:75 (AD5075) and complexed with plasmid, pTRAIL-EGFP. AD liposome/pTRAIL-EGFP were evaluated for their complex ability, particle size, polydispersity index, zeta potential, expression of pTRAIL-EGFP, cytotoxicity, cell growth inhibition and apoptosis induction in KB cells. AD liposomes complexed completely with pTRAIL-EGFP at AD liposome/DNA ratios of above 4.5/1. The particle size of AD liposome/pTRAIL-EGFP ranged from 180 ± 8 to 1,072 ± 657 nm depending on the proportion of lipid composition and liposome/DNA ratio. The extent of gene expression of pTRAIL-EGFP via AD liposome/pTRAIL-EGFP was significantly higher than that of the cells treated with pTRAIL-EGFP and depended on the AD liposome/DNA ratio. Cytotoxicity of AD liposomes was dependent on A and D molar ratio. Cell growth inhibition of AD liposome/pTRAIL-EGFP was significantly higher than that of the cells treated with pTRAIL-EGFP. The amount of late apoptotic and dead cells of AD liposome/pTRAIL-EGFP was significantly higher than that of cells treated with pTRAIL-EGFP. From this study that one can conclude that AD liposomes can carry and deliver pTRAIL-EGFP into KB cells resulting in cell growth inhibition and cell death.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"368-377"},"PeriodicalIF":3.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9188610","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}
Pub Date : 2023-12-01Epub Date: 2023-03-28DOI: 10.1080/08982104.2023.2190810
Shi-Yi Xu, Wei-Wei Wang, Zi-Hui Qu, Xiang-Ke Zhang, Ming Chen, Xin-Yu Zhang, Nan-Nan Xing, Hui Su, Xue-Ying Wang, Ming-Yu Cui, Xue-Ying Yan, Wei Ma
Co-loading doxorubicin (DOX) and Schizandrin A (SchA) long-circulating liposome (SchA-DOX-Lip) have been confirmed to have good antitumor activity in vitro. However, in vivo pharmacodynamics, targeting, safety, and mechanism of action of SchA-DOX-Lip still need to be further verified. We investigated the tumor inhibition effect, targeting, safety evaluation, and regulation of tumor apoptosis-related proteins of the SchA-DOX-Lip. MTT assay was used to investigate the inhibitory effect of SchA-DOX-Lip on CBRH7919 cells. The drug uptake of CBRH7919 cells was observed by inverted fluorescence microscope. The tumor-bearing nude mice models of CBRH7919 were established, and the anti-tumor effect of SchA-DOX-Lip in vivo was evaluated by tumor biological observation, H&E staining, and TUNEL staining. The distribution and targeting of SchA-DOX-Lip in nude mice models were investigated by small animal imaging and tissue distribution experiment of CBRH7919. The biosafety of SchA-DOX-Lip was evaluated by blood routine parameters, biochemical indexes, and H&E staining. The expression of tumor-associated apoptotic proteins (Bcl-2, Bax, and Caspase-3) was detected by immunohistochemistry anvd western blotting. The results showed that SchA-DOX-Lip had cytotoxicity to CBRH7919 cells which effectively inhibited the proliferation of CBRH7919 cells, improved the uptake of drugs by CBRH7919 cells and the targeting effect of drugs on tumor site. H&E staining and biochemical detection results showed that SchA-DOX-Lip had high biosafety and did not cause serious damage to normal tissues. Western-blotting and TUNEL staining results showed that SchA-DOX-Lip could improve the regulatory effect of drugs on tumor apoptosis proteins. It was demonstrated that SchA-DOX-Lip had high safety and strong tumor inhibition effects, providing a new method for the clinical treatment of hepatocellular carcinoma (HCC).
{"title":"Long-circulating doxorubicin and Schizandrin A liposome with drug-resistant liver cancer activity: <i>in vitro</i> and <i>in vivo</i> evaluation.","authors":"Shi-Yi Xu, Wei-Wei Wang, Zi-Hui Qu, Xiang-Ke Zhang, Ming Chen, Xin-Yu Zhang, Nan-Nan Xing, Hui Su, Xue-Ying Wang, Ming-Yu Cui, Xue-Ying Yan, Wei Ma","doi":"10.1080/08982104.2023.2190810","DOIUrl":"10.1080/08982104.2023.2190810","url":null,"abstract":"<p><p>Co-loading doxorubicin (DOX) and Schizandrin A (SchA) long-circulating liposome (SchA-DOX-Lip) have been confirmed to have good antitumor activity <i>in vitro</i>. However, <i>in vivo</i> pharmacodynamics, targeting, safety, and mechanism of action of SchA-DOX-Lip still need to be further verified. We investigated the tumor inhibition effect, targeting, safety evaluation, and regulation of tumor apoptosis-related proteins of the SchA-DOX-Lip. MTT assay was used to investigate the inhibitory effect of SchA-DOX-Lip on CBRH7919 cells. The drug uptake of CBRH7919 cells was observed by inverted fluorescence microscope. The tumor-bearing nude mice models of CBRH7919 were established, and the anti-tumor effect of SchA-DOX-Lip <i>in vivo</i> was evaluated by tumor biological observation, H&E staining, and TUNEL staining. The distribution and targeting of SchA-DOX-Lip in nude mice models were investigated by small animal imaging and tissue distribution experiment of CBRH7919. The biosafety of SchA-DOX-Lip was evaluated by blood routine parameters, biochemical indexes, and H&E staining. The expression of tumor-associated apoptotic proteins (Bcl-2, Bax, and Caspase-3) was detected by immunohistochemistry anvd western blotting. The results showed that SchA-DOX-Lip had cytotoxicity to CBRH7919 cells which effectively inhibited the proliferation of CBRH7919 cells, improved the uptake of drugs by CBRH7919 cells and the targeting effect of drugs on tumor site. H&E staining and biochemical detection results showed that SchA-DOX-Lip had high biosafety and did not cause serious damage to normal tissues. Western-blotting and TUNEL staining results showed that SchA-DOX-Lip could improve the regulatory effect of drugs on tumor apoptosis proteins. It was demonstrated that SchA-DOX-Lip had high safety and strong tumor inhibition effects, providing a new method for the clinical treatment of hepatocellular carcinoma (HCC).</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"338-352"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9971950","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}
Pub Date : 2023-09-01DOI: 10.1080/08982104.2022.2162539
Changzhao Jiang, Rui Ma, Xiumei Jiang, Renhua Fang, Jincui Ye
Objective: In this work, a propranolol hydrochloride (PRH) transfersomes loaded cutaneous hydrogel patch was developed for topical drug delivery in the affected area of infantile haemangioma.
Methods: Sodium cholate was used as the edge activator to prepare the transfersomes. Based on the central composite design, transfersomes hydrogel patch formulation was optimised with 48 h cumulative penetration and time lag as response values. Particle sizes and morphology of the prepared transfersomes were assessed. They were loaded in a cutaneous hydrogel patch, after which their skin permeation abilities were evaluated, and histopathological effects were investigated using guinea pigs. Moreover, in vivo pharmacokinetics studies were performed in rats.
Results: The transfersomes system had a encapsulation efficiency of 81.84 ± 0.53%, particle size of 186.8 ± 3.38 nm, polydispersity index of 0.186 ± 0.002, and a zeta potential of -28.6 ± 2.39 mV. Transmission electron microscopy images revealed sphericity of the particles. The ex vivo drug's penetration of the optimised transfersomes hydrogel patch was 111.05 ± 11.97 μg/cm2 through rat skin within 48 h. Assessment of skin tissue did not reveal any histopathological alterations in epidermal and dermal cells. Pharmacokinetic studies showed that skin Cmax (68.22 μg/cm2) and AUC0-24 (1007.33 μg/cm2 × h) for PRH transfersomes hydrogel patch were significantly higher than those of commercially available oral dosage form and hydrogel patch without transfersomes. These findings imply that the transfersomes hydrogel patch can prolong drug accumulation in the affected skin area, and reduce systemic drug distribution via the blood stream.
Conclusions: The hydrogel patch-loaded PRH transfersomes is a potentially useful drug formulation for infantile haemangioma.
{"title":"A transfersomes hydrogel patch for cutaneous delivery of propranolol hydrochloride: formulation, <i>in vitro</i>, <i>ex vivo</i> and <i>in vivo</i> studies.","authors":"Changzhao Jiang, Rui Ma, Xiumei Jiang, Renhua Fang, Jincui Ye","doi":"10.1080/08982104.2022.2162539","DOIUrl":"https://doi.org/10.1080/08982104.2022.2162539","url":null,"abstract":"<p><strong>Objective: </strong>In this work, a propranolol hydrochloride (PRH) transfersomes loaded cutaneous hydrogel patch was developed for topical drug delivery in the affected area of infantile haemangioma.</p><p><strong>Methods: </strong>Sodium cholate was used as the edge activator to prepare the transfersomes. Based on the central composite design, transfersomes hydrogel patch formulation was optimised with 48 h cumulative penetration and time lag as response values. Particle sizes and morphology of the prepared transfersomes were assessed. They were loaded in a cutaneous hydrogel patch, after which their skin permeation abilities were evaluated, and histopathological effects were investigated using guinea pigs. Moreover, in vivo pharmacokinetics studies were performed in rats.</p><p><strong>Results: </strong>The transfersomes system had a encapsulation efficiency of 81.84 ± 0.53%, particle size of 186.8 ± 3.38 nm, polydispersity index of 0.186 ± 0.002, and a zeta potential of -28.6 ± 2.39 mV. Transmission electron microscopy images revealed sphericity of the particles. The <i>ex vivo</i> drug's penetration of the optimised transfersomes hydrogel patch was 111.05 ± 11.97 μg/cm<sup>2</sup> through rat skin within 48 h. Assessment of skin tissue did not reveal any histopathological alterations in epidermal and dermal cells. Pharmacokinetic studies showed that skin <i>C</i><sub>max</sub> (68.22 μg/cm<sup>2</sup>) and AUC<sub>0-24</sub> (1007.33 μg/cm<sup>2</sup> × h) for PRH transfersomes hydrogel patch were significantly higher than those of commercially available oral dosage form and hydrogel patch without transfersomes. These findings imply that the transfersomes hydrogel patch can prolong drug accumulation in the affected skin area, and reduce systemic drug distribution via the blood stream.</p><p><strong>Conclusions: </strong>The hydrogel patch-loaded PRH transfersomes is a potentially useful drug formulation for infantile haemangioma.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":"33 3","pages":"258-267"},"PeriodicalIF":4.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9870189","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}