Journal of Liposome Research最新文献_第4页

Liposome-enabled bufalin and doxorubicin combination therapy for trastuzumab-resistant breast cancer with a focus on cancer stem cells. 脂质体驱动的布法林和多柔比星联合疗法治疗曲妥珠单抗耐药的乳腺癌，重点关注癌症干细胞。

IF 4.4 4区医学

Journal of Liposome Research Pub Date : 2024-09-01 Epub Date: 2024-01-25 DOI: 10.1080/08982104.2024.2305866

Yu Gao, Andrew N Shelling, Emma Nolan, David Porter, Euphemia Leung, Zimei Wu

{"title":"Liposome-enabled bufalin and doxorubicin combination therapy for trastuzumab-resistant breast cancer with a focus on cancer stem cells.","authors":"Yu Gao, Andrew N Shelling, Emma Nolan, David Porter, Euphemia Leung, Zimei Wu","doi":"10.1080/08982104.2024.2305866","DOIUrl":"10.1080/08982104.2024.2305866","url":null,"abstract":"Breast cancer stem cells (BCSCs) play a key role in therapeutic resistance in breast cancer treatments and disease recurrence. This study aimed to develop a combination therapy loaded with pH-sensitive liposomes to kill both BCSCs and the okbulk cancer cells using trastuzumab-sensitive and resistant human epidermal growth factor receptor 2 positive (HER2+) breast cancer cell models. The anti-BCSCs effect and cytotoxicity of all-trans retinoic acid, salinomycin, and bufalin alone or in combination with doxorubicin were compared in HER2+ cell line BT-474 and a validated trastuzumab-resistant cell line, BT-474R. The most potent anti-BCSC agent was selected and loaded into a pH-sensitive liposome system. The effects of the liposomal combination on BCSCs and bulk cancer cells were assessed. Compared with BT-474, the aldehyde dehydrogenase positive BCSC population was elevated in BT-474R (3.9 vs. 23.1%). Bufalin was the most potent agent and suppressed tumorigenesis of BCSCs by ∼50%, and showed strong synergism with doxorubicin in both BT-474 and BT-474R cell lines. The liposomal combination of bufalin and doxorubicin significantly reduced the BCSC population size by 85%, and inhibited both tumorigenesis and self-renewal, although it had little effect on the migration and invasiveness. The cytotoxicity against the bulk cancer cells was also enhanced by the liposomal combination than either formulation alone in both cell lines (p < 0.001). The liposomal bufalin and doxorubicin combination therapy may effectively target both BCSCs and bulk cancer cells for a better outcome in trastuzumab-resistant HER2+ breast cancer.","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"489-506"},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546604","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}

引用次数: 0

Process development of inhalation powders containing simvastatin loaded liposomes using spray drying technology. 喷雾干燥法制备辛伐他汀脂质体吸入粉剂的工艺研究。

IF 4.4 4区医学

Journal of Liposome Research Pub Date : 2024-09-01 Epub Date: 2023-12-03 DOI: 10.1080/08982104.2023.2287588

Cristina-Ioana Barbălată, Alina Silvia Porfire, Rita Ambrus, Mahwash Mukhtar, Árpád Farkas, Ioan Tomuță

{"title":"Process development of inhalation powders containing simvastatin loaded liposomes using spray drying technology.","authors":"Cristina-Ioana Barbălată, Alina Silvia Porfire, Rita Ambrus, Mahwash Mukhtar, Árpád Farkas, Ioan Tomuță","doi":"10.1080/08982104.2023.2287588","DOIUrl":"10.1080/08982104.2023.2287588","url":null,"abstract":"The development of an inhalation powder (IP) for cancer therapy is desired to improve the therapeutic response and patient compliance. The latest studies highlighted that statins, a class of drugs used in hypercholesterolemia, can have anticancer and antiinflammatory properties. Therefore, the aim of the study was to develop an IP containing liposomes loaded with simvastatin using spray drying technology, as well as to investigate the influence of formulation factors on the quality attributes of the IP by means of experimental design. Results highlighted that the composition of liposomes, namely type of phospholipid and cholesterol concentration, highly influences the quality attributes of IP, and the use of optimal concentrations of excipients, i.e. D-mannitol and L-leucine, is essential to preserve the characteristics of liposomes throughout the spray drying process. The in vitro characterization of the optimal IP formulation revealed that the total percentage of released drug is higher from the IP formulation compared to the powder of active substance (53.38 vs. 42.76%) over a period of six hours, and 39.67% of dry particles have a size less than 5 µm, making them suitable for inhalation. As a conclusion, spray drying technology can be effectively used in the development and preparation of IP containing liposomes.","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"421-434"},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299249","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}

引用次数: 0

Sialic acid-modified doxorubicin liposomes target tumor-related immune cells to relieve multiple inhibitions of CD8⁺ T cells. 唾液酸修饰的多柔比星脂质体靶向肿瘤相关免疫细胞，缓解 CD8+ T 细胞的多重抑制。

IF 4.4 4区医学

Journal of Liposome Research Pub Date : 2024-09-01 Epub Date: 2024-01-09 DOI: 10.1080/08982104.2023.2298901

Zhouchunxiao Du, Dezhi Sui, Dongzhe Xin, Xueying Tang, Mingze Li, Xinrong Liu, Yihui Deng, Yanzhi Song

{"title":"Sialic acid-modified doxorubicin liposomes target tumor-related immune cells to relieve multiple inhibitions of CD8+ T cells.","authors":"Zhouchunxiao Du, Dezhi Sui, Dongzhe Xin, Xueying Tang, Mingze Li, Xinrong Liu, Yihui Deng, Yanzhi Song","doi":"10.1080/08982104.2023.2298901","DOIUrl":"10.1080/08982104.2023.2298901","url":null,"abstract":"In different types of cancer treatments, cancer-specific T cells are required for effective anticancer immunity, which has a central role in cancer immunotherapy. However, due to the multiple inhibitions of CD8+ T cells by tumor-related immune cells, CD8+ T-cell mediated antitumor immunotherapy has not achieved breakthrough progress in the treatment of solid tumors. Receptors for sialic acid (SA) are highly expressed in tumor-associated immune cells, so SA-modified nanoparticles are a drug delivery nanoplatform using tumor-associated immune cells as vehicles. To relieve the multiple inhibitions of CD8+ T cells by tumor-associated immune cells, we prepared SA-modified doxorubicin liposomes (SL-DOX, Scheme 1A). In our study, free SA decreased the toxicity of SL-DOX to tumor-associated immune cells. Compared with common liposomes, SL-DOX could inhibit tumor growth more effectively. It is worth noting that SL-DOX could not only kill tumor-related neutrophils and monocytes to relieve the multiple inhibitions of CD8+ T cells but also induce immunogenic death of tumor cells to promote the infiltration and differentiation of CD8+ T cells (Scheme 1B). Therefore, SL-DOX has potential value for the clinical therapeutic effect of CD8+ T cells mediating anti-tumor immunotherapy.","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"464-474"},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403154","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}

引用次数: 0

Synergistic antibacterial effect of the pistachio green hull extract-loaded porphysome decorated with 4-nitroimidazole against bacteria. 用 4-硝基咪唑装饰的开心果绿壳提取物负载孔隙体对细菌的协同抗菌效果。

IF 4.4 4区医学

Journal of Liposome Research Pub Date : 2024-09-01 Epub Date: 2024-01-22 DOI: 10.1080/08982104.2024.2304755

Nastaran Mahafel, Zahra Vaezi, Mohsen Barzegar, Azadeh Hekmat, Hossein Naderi-Manesh

{"title":"Synergistic antibacterial effect of the pistachio green hull extract-loaded porphysome decorated with 4-nitroimidazole against bacteria.","authors":"Nastaran Mahafel, Zahra Vaezi, Mohsen Barzegar, Azadeh Hekmat, Hossein Naderi-Manesh","doi":"10.1080/08982104.2024.2304755","DOIUrl":"10.1080/08982104.2024.2304755","url":null,"abstract":"'Active targeting' refers to modifying a nanocarrier's surface with targeting ligands. This study introduced an efficient approach for immobilizing imidazole-based drugs onto the metallated-porphyrin complex within the porphysome nanocarrier. To enhance cellular and bacterial uptake, a Ni-porphyrin with a fatty acid tail was synthesized and placed in the bilayer center of DPPC, facilitating receptor-mediated endocytosis. The Ni-porphyrin in the head group of the Ni-porphyrin-tail was placed superficially in the polar region of the membrane. Spherical unilamellar vesicle formation (DPPC: Ni-porphyrin-tail 4:1 mole ratio), as metallo-porphysome, was achieved through supramolecular self-assembly in an aqueous buffer. These vesicles exhibited a diameter of 279 ± 7 nm and a zeta potential of -15.3 ± 2.5 mV, showcasing their unique cytocompatibility. Nitroimidazole was decorated on the surface of metallo-porphysomes and pistachio green hull extract (PGHE) was loaded into the carrier for synergistic activity against (E. coli) and (S. aureus) bacteria strains. The physicochemical properties of Nitroimidazole-porphysome-PGHE, including size, zeta potential, morphology, loading efficiency, and release profile under various pH and temperature conditions in simulated gastrointestinal fluids were characterized. This combination therapy prevented bacterial cell attachment and biofilm formation in Caco-2 cells, as colon epithelial cells. The remarkable benefit of this system is that it does not affect cell viability even at 0.5 mg/ml. This study demonstrates the potential of a new co-delivery system using biocompatible metallo-porphysomes to decrease bacterial infections.","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"475-488"},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512739","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}

引用次数: 0

Development of a brain-targeted nano drug delivery system to enhance the treatment of neurodegenerative effects of resveratrol. 脑靶向纳米给药系统的开发以增强白藜芦醇对神经退行性作用的治疗。

IF 4.4 4区医学

Journal of Liposome Research Pub Date : 2024-09-01 Epub Date: 2023-12-07 DOI: 10.1080/08982104.2023.2290050

Yang Yu, Shutong Li, Liang Kong, Yumeng Du, Yang Liu, Juan Zang, Ruibo Guo, Lu Zhang, Ziyue Zhao, Ruijun Ju, Xuetao Li

{"title":"Development of a brain-targeted nano drug delivery system to enhance the treatment of neurodegenerative effects of resveratrol.","authors":"Yang Yu, Shutong Li, Liang Kong, Yumeng Du, Yang Liu, Juan Zang, Ruibo Guo, Lu Zhang, Ziyue Zhao, Ruijun Ju, Xuetao Li","doi":"10.1080/08982104.2023.2290050","DOIUrl":"10.1080/08982104.2023.2290050","url":null,"abstract":"As the aging population continues to increase, aging-related inflammation, oxidative stress, and neurodegenerative diseases have become serious global health threats. Resveratrol, a star molecule in natural polyphenols, has been widely reported to have physiological activities such as anti-aging, anti-inflammatory, antioxidant, and neuroprotection. However, its poor water solubility, rapid metabolism, low bioavailability and poor targeting ability, which limits its application. Accordingly, a brain-targeted resveratrol liposome (ANG-RES-LIP) was developed to solve these issues. Experimental results showed that ANG-RES-LIP has a uniform size distribution, good biocompatibility, and a drug encapsulation rate of over 90%. Furthermore, in vitro cell experiments showed that the modification of the targeting ligand ANG significantly increased the capability of RES to cross the BBB and neuronal uptake. Compared with free RES, ANG-RES-LIP demonstrated stronger antioxidant activity and the ability to rescue oxidatively damaged cells from apoptosis. Additionally, ANG-RES-LIP showed the ability to repair damaged neuronal mitochondrial membrane potential. In vivo experiments further demonstrated that ANG-RES-LIP improved cognitive function by reducing oxidative stress and inflammation levels in the brains of aging model mice, repairing damaged neurons and glial cells, and increasing brain-derived neurotrophic factor. In summary, this study not only provides a new method for further development and application of resveratrol but also a promising strategy for preventing and treating age-related neurodegenerative diseases.","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"435-451"},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460335","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}

引用次数: 0

Dyeing of polyacrylonitrile knitted fabric using liposomes. 使用脂质体对聚丙烯腈针织物进行染色。

IF 3.6 4区医学

Journal of Liposome Research Pub Date : 2024-08-26 DOI: 10.1080/08982104.2024.2396107

Rıza Atav, Selin Güler Köylüoğlu, Aminoddin Haji, Uğur Ergünay

{"title":"Dyeing of polyacrylonitrile knitted fabric using liposomes.","authors":"Rıza Atav, Selin Güler Köylüoğlu, Aminoddin Haji, Uğur Ergünay","doi":"10.1080/08982104.2024.2396107","DOIUrl":"https://doi.org/10.1080/08982104.2024.2396107","url":null,"abstract":"In this study, it was aimed to analyze the effects of liposomes on the dyeing of polyacrylonitrile fabrics. For this purpose, firstly liposome synthesis was carried out, and then liposome production was confirmed by Fourier transform infrared spectroscopy analysis. Additionally, zeta potential measurements were carried out to see whether stable structures were formed. Then, a selected basic dye was encapsulated with a liposome and the possibilities of using these capsules as alternative to retarders in the dyeing of polyacrylonitrile fabrics were examined. According to results obtained, it can be said that the 1% solution of synthesized liposomes creates a more stable suspension with a polydispersity index of 0.472 and the average particle size of 165.2 nm. On the other hand, it has been revealed that if 1% liposome is used in dyeing, a kind of retarder effect can be achieved in the dyeing of polyacrylonitrile fabrics. Moreover, it can be said that the decrease in color efficiency, that is, the loss of yield, caused by the use of liposome at the end of dyeing is lower compared to the retarder. This is also a very important issue, because a good retarder is expected to slow down the dye uptake, but not reduce the dye intake too much at the end of the dyeing. Dyeing levelness (%) was found to be 96.1, 97.4, and 97.1 for dyeings without auxiliary, with 1% cationic retarder and with 1% liposome, respectively. Beyond this, no significant difference was observed in terms of fastness of dyeing.","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-9"},"PeriodicalIF":3.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055814","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}

引用次数: 0

Sialic acid-modified docetaxel cationic liposomes: double targeting of tumor-associated macrophages and tumor endothelial cells. 唾液酸修饰的多西他赛阳离子脂质体：双重靶向肿瘤相关巨噬细胞和肿瘤内皮细胞。

IF 3.6 4区医学

Journal of Liposome Research Pub Date : 2024-08-13 DOI: 10.1080/08982104.2024.2388140

Tiantian Guo, Yu Wang, Dazhi Wang, Ruirui Ge, Zhouchunxiao Du, Zhirong Zhang, Yushi Qin, Xinrong Liu, Yihui Deng, Yanzhi Song

{"title":"Sialic acid-modified docetaxel cationic liposomes: double targeting of tumor-associated macrophages and tumor endothelial cells.","authors":"Tiantian Guo, Yu Wang, Dazhi Wang, Ruirui Ge, Zhouchunxiao Du, Zhirong Zhang, Yushi Qin, Xinrong Liu, Yihui Deng, Yanzhi Song","doi":"10.1080/08982104.2024.2388140","DOIUrl":"https://doi.org/10.1080/08982104.2024.2388140","url":null,"abstract":"Taxane drugs are clinically used for the treatment of many types of cancers due to their excellent antitumor effects. However, the surfactants contained in the injections currently used in the clinic may have serious toxic side effects on the organism, making it necessary to develop new dosage forms. Cationic liposomes have been widely used in antitumor research because of their advantage of preferentially targeting tumor neovascularization, but antitumor by targeting tumor vasculature alone does not necessarily provide good results. Malignant tumors represent complex ecosystems, tumor-associated macrophages (TAMs) and tumor endothelial cells (TECs) in the tumor microenvironment play crucial roles in tumor growth. Therefore, given the ability to achieve active targeting of TAMs and TECs by using sialic acid (SA) as a targeting material, the potential of cationic nanoformulations to preferentially target neovascularization at the tumor site, and the excellent antitumor effects of the taxane drugs docetaxel (DOC), in the present study, sialic acid-cholesterol coupling (SA-CH) was selected as a targeting material to prepare a DOC cationic liposome (DOC-SAL) for tumor therapy. The results of the study showed that DOC-SAL had the strongest drug accumulation in tumor tissues compared with the common DOC formulations, and was able to effectively reduce the colonization of TAMs, inhibit the proliferation of tumor cells, and have the best tumor-suppressing effect. In addition, DOC-SAL was able to improve the internal microenvironment of tumors by modulating cytokines. In summary, this drug delivery system has good anti-tumor effects and provides a new option for tumor therapy.","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975884","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}

引用次数: 0

Micro-scale quantitative analysis of sterol content in liposomes. 脂质体中固醇含量的微尺度定量分析。

IF 3.6 4区医学

Journal of Liposome Research Pub Date : 2024-08-12 DOI: 10.1080/08982104.2024.2388146

Laura Charlotte Paweletz, Norman Labedzki, Thomas Günther Pomorski

{"title":"Micro-scale quantitative analysis of sterol content in liposomes.","authors":"Laura Charlotte Paweletz, Norman Labedzki, Thomas Günther Pomorski","doi":"10.1080/08982104.2024.2388146","DOIUrl":"https://doi.org/10.1080/08982104.2024.2388146","url":null,"abstract":"The high complexity of biological membranes has driven the development and application of a wide range of model membrane systems. Among these models, liposomes are extensively used because of their versatility in mimicking cellular membranes with a wide range of lipid compositions. However, the accurate quantification of lipid components, such as sterols, within these models remains a critical requirement for validation, data interpretation, and comparison. Here, we present a reliable and sensitive colorimetric assay using the Zak color reaction, which we have specifically adapted for the quantification of sterols at the micro-scale level. The assay was evaluated using cholesterol, ergosterol, and sitosterol standards, reflecting the diversity of sterol species across organisms. The reaction mechanism involves the dehydration of sterols to form carbonium ions, which are oxidized to form various enylic carbonium ions with specific absorption peaks. Due to the different chemical structures of cholesterol, ergosterol, and sitosterol, the resulting spectra show that the colored reaction products are formed in different proportions. The stability and interconversion of these species over time were analyzed. Cholesterol and sitosterol showed a clear peak at 555 nm, while ergosterol had prominent peaks at shorter wavelengths. Sterol assays on liposomal preparations showed accurate sterol incorporation with minimal loss during processing steps. These results demonstrate that this assay provides a robust and accurate measurement of sterol content in large unilamellar vesicles, making it a valuable tool for liposomal studies.","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-8"},"PeriodicalIF":3.6,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971253","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}

引用次数: 0

Effect of size and pH-sensitivity of liposomes on cellular uptake pathways and pharmacokinetics of encapsulated gemcitabine. 脂质体的大小和 pH 敏感性对包裹吉西他滨的细胞摄取途径和药代动力学的影响

IF 3.6 4区医学

Journal of Liposome Research Pub Date : 2024-08-09 DOI: 10.1080/08982104.2024.2389969

Mingtan Tang, Sasi Bhushan Yarragudi, Patrick Pan, Kaiyun Yang, Manju Kanamala, Zimei Wu

{"title":"Effect of size and pH-sensitivity of liposomes on cellular uptake pathways and pharmacokinetics of encapsulated gemcitabine.","authors":"Mingtan Tang, Sasi Bhushan Yarragudi, Patrick Pan, Kaiyun Yang, Manju Kanamala, Zimei Wu","doi":"10.1080/08982104.2024.2389969","DOIUrl":"https://doi.org/10.1080/08982104.2024.2389969","url":null,"abstract":"To enhance cytoplasmic delivery efficiency, pH-sensitive liposomes (PSL) have been proposed as a novel strategy. To facilitate clinical translation, this study aims to understand the impact of both size and pH-sensitivity on cellular uptake pathways, intracellular trafficking and pharmacokinetics of liposomes. The large liposomes (130-160 nm) were prepared using thin-film hydration method, while small liposomes (∼60 nm) were fabricated using microfluidics, for both PSL and non-pH-sensitive liposomes (NPSL). Cellular uptake pathways and intracellular trafficking was investigated through confocal imaging with aid of various endocytosis inhibitors. Intracellular gemcitabine delivery by various liposomal formulations was quantified using HPLC, and the cytotoxicity was assessed via cell viability assays. Pharmacokinetics of gemcitabine loaded in various liposomes was evaluated in rats following intravenous administration. Larger liposomes had a higher loading capacity for hydrophilic gemcitabine (7% vs 4%). Small PSL exhibited superior cellular uptake compared to large PSL or NPSLs. Moreover, the alkalization of endosomes significantly attenuated the cellular uptake of PSL. Large liposomes (PSL and NPSL) predominantly entered cells via clathrin-dependent pathway, whereas small liposomes partially utilized caveolae-dependent pathway. However, the long circulation of the liposomes, as measured by the encapsulated gemcitabine, was compromised by both pH-sensitivity and size reduction (9.5 h vs 5.3 h). Despite this drawback, our results indicate that small PSL holds promise as vectors for the next generation of liposomal nanomedicine, owing to their superior cytoplasmic delivery efficiency.","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-11"},"PeriodicalIF":3.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912980","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}

引用次数: 0

Precision-engineered PEGylated liposome for dual payload delivery: enhancing efficacy of Doxorubicin hydrochloride and miR-145 mimics in breast cancer cells. 精准设计的 PEG 化脂质体用于双重有效载荷递送：提高盐酸多柔比星和 miR-145 模拟物在乳腺癌细胞中的疗效。

IF 3.6 4区医学

Journal of Liposome Research Pub Date : 2024-08-05 DOI: 10.1080/08982104.2024.2385457

Chu Xin Ng, Chee Wun How, Sau Har Lee

{"title":"Precision-engineered PEGylated liposome for dual payload delivery: enhancing efficacy of Doxorubicin hydrochloride and miR-145 mimics in breast cancer cells.","authors":"Chu Xin Ng, Chee Wun How, Sau Har Lee","doi":"10.1080/08982104.2024.2385457","DOIUrl":"https://doi.org/10.1080/08982104.2024.2385457","url":null,"abstract":"Micro-145 down-regulation is frequently found in breast cancers, indicating its potential as a therapeutic target. The introduction of exogenous miR-145 directly to the tumor sites has been a hurdle due to limited delivery, low bioavailability, and hence lower therapeutic efficacy. Thus, this study aims to synthesize and characterize PEGylated liposome co-loaded with Dox-HCl and miR-145 mimics to investigate its in-vitro anti-proliferative activity against MDA-MB-231 cells. The formulations were developed using a composite central design to optimize nanoparticle size and encapsulation efficiency (EE%) of Dox-HCl and miR-145 mimics. The optimized formulation exhibited the highest desirability function (D = 0.814) and displayed excellent stability over 60 days at 4 °C, maintaining a stable nanoparticle size and zeta potential, with relative EE% of Dox-HCl and miR-145 mimics on the final incubation day 94.97 ± 0.53% and 51.96 ± 2.67%, respectively. The system displayed a higher rate of drug release within 4 h of incubation at an acidic condition. Additionally, the optimized formulation demonstrated a higher toxicity (IC50 = 0.58 μM) against MDA-MB-231 cells than the free Dox- HCl and miR-145 regimen (IC50 = 1.00 μM). Our findings suggest that PEGylated liposome is tunable for effective concurrent delivery of anticancer drugs and therapeutic miRNAs into tumor cells, necessitating further investigation.","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889441","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}

引用次数: 0