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Ph sensitive liposomes

Juliana de Oliveira Silva, Sued Eustáquio Mendes Miranda, Elaine Amaral Leite, Adriano de Paula Sabino, Karina Braga Gomes Borges, Valbert Nascimento Cardoso, Geovanni Dantas Cassali, Andrea Grabe Guimarães, Mônica Cristina Oliveira, André Luis Branco de Barros
Doxorubicin (DOX) is widely used in cancer treatment, however, the use of this drug is often limited due to its cardiotoxic side effects. In order to avoid these adverse effects, the encapsulation of DOX into nanosystems has been used in the last decades. In this context, pH-sensitive liposomes have been shown promising for delivering cytotoxic agents into tumor cells, however, the lack of information about in vivo toxicity of this nanocarrier has impaired translational studies. Therefore, the aim of this work was to investigate the acute toxicity and cardiotoxicity of DOX-loading pH-sensitive liposomes (SpHL-DOX)...
June 1, 2018: Toxicology and Applied Pharmacology
Yi-Ting Chiang, Sih-Ying Lyu, Yu-Han Wen, Chun-Liang Lo
pH-sensitive polymer⁻liposomes can rapidly release their payloads. However, it is difficult to simultaneously achieve stability and pH-responsiveness in the polymer⁻liposomes. In this study, stable and pH-sensitive crosslinked polymer⁻liposomes were fabricated through electrostatic interactions. The pH-sensitive copolymer methoxy poly(ethylene glycol)- block -poly(methacrylic acid)-cholesterol (mPEG- b -P(MAAc)-chol) and crosslinking reagent poly(ethylene glycol) with end-capped with lysine (PEG-Lys2) were synthesized and characterized...
May 30, 2018: International Journal of Molecular Sciences
Chunyan Hou, Hu Bai, Zhaojie Wang, Yuanhao Qiu, Li-Li Kong, Feifei Sun, Dongdong Wang, Hong Yin, Xiaoli Zhang, Haibo Mu, Jinyou Duan
Accompanied by overproduction of oxidants and reduction of pH, inflammation is closely related to many diseases such as cancer, atherosclerosis, and asthma. Besides chemotherapeutic agents, the potential regulative role of autophagy in inflammation is being actively investigated. RNA interference (RNAi)-based gene therapy is widely explored for clinical therapy but seriously restricted by lack of suitable carriers. In this study, we synthesized a hyaluronan-based ROS-sensitive polymer which was expected to release loaded chemical drugs in inflammatory environment and further developed a stable and nontoxic co-delivery nanosystem of siRNA targeting autophagy suppressive gene and chemotherapeutic agents...
September 1, 2018: Carbohydrate Polymers
Man Li, Kairong Shi, Xian Tang, Jiaojie Wei, Xingli Cun, Yang Long, Zhirong Zhang, Qin He
Cancer associated fibroblasts (CAFs) which shape the tumor microenvironment (TME) and the presence of blood brain barrier (BBB) remain great challenges in targeting breast cancer and its brain metastasis. Herein, we reported a strategy using PTX-loaded liposome co-modified with acid-cleavable folic acid (FA) and BBB transmigrating cell penetrating peptide dNP2 peptide (cFd-Lip/PTX) for enhanced delivery to orthotopic breast cancer and its brain metastasis. Compared with single ligand or non-cleavable Fd modified liposomes, cFd-Lip exhibited synergistic TME targeting and BBB transmigration...
May 22, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Xian Li, Xiudan Wang, Luping Sha, Da Wang, Wei Shi, Qinfu Zhao, Siling Wang
Thermo-chemotherapy exhibits a synergistic therapeutic efficiency for cancer, and the sensitivity of cancer cells to chemical drugs could be increased to a large extent at elevated temperature. In this work, a novel biocompatible drug delivery system TSMCN was designed by covering a liposome on the surface of the mesoporous carbon nanoparticles (MCN). The TSMCN had good photothermal efficiency and photostability. The DOX loaded TSMCN (DOX/TSMCN) showed a slower release than DOX loaded MCN-COOH (DOX/MCN-COOH) both in simulated tumor environment (pH 5...
May 25, 2018: ACS Applied Materials & Interfaces
Virgínia M Gouveia, José Lopes-de-Araújo, Sofia A Costa Lima, Cláudia Nunes, Salette Reis
AIM: The treatment of rheumatoid arthritis remains a challenge as available therapies still entail the risk of deleterious off-target effects. The present study describes hyaluronic acid-conjugated pH-sensitive liposomes as an effective drug delivery-targeting strategy to synovial cells. MATERIALS & METHODS: Therapeutic, cytotoxic and targeting potential of developed liposomes were studied in vitro using macrophages and fibroblasts cell lines. RESULTS & CONCLUSION: Results suggest an enhanced cellular uptake of conjugated liposomes, mainly mediated by caveolae- and clathrin-dependent endocytosis...
May 2018: Nanomedicine
Thi Tuong Vy Phan, Madhappan Santha Moorthy, Hyun Wook Kang, Seung Yun Nam, Yong Wook Lee, Junghwan Oh
Magnetoliposomes (ML) have been emerging as a novel multifunctional nanoparticle with a wide range of biomedical and therapeutic applications over the past decade. Although the ML system has shown excellent performances, the stability and lipid peroxidation of liposomal components are still remaining as key issues and need to be solved for intensive applications. Changing zeta potential of nanoparticles' surface can be seen as a potential way to achieve the stable dispersion. In this work, we have employed the positive charged, abundant and cheap chitosan to coat ML in order to change the zeta potential of the ML system and examined the stability of chitosan@magnetoliposomes (CML) in long-term storage...
January 1, 2018: Journal of Nanoscience and Nanotechnology
Hiroto Hatakeyama
 Nucleic acid therapy is expected to be a next generation medicine. We recently developed a multifunctional envelope-type nano device (MEND) for use as a novel delivery system. The modification of polyethylene glycol (PEG), i.e., PEGylation, is useful for achieving the delivery of MENDs to tumors via an enhanced permeability and retention (EPR) effect. However, PEGylation strongly inhibits the cellular uptake and endosomal escape of MEND, which results in significant loss of action, and therefore lost effectiveness, of the cargo therapeutic...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Liziane O F Monteiro, Ângelo Malachias, Gwenaelle Pound-Lana, Rogério Magalhães-Paniago, Vanessa C F Mosqueira, Mônica C Oliveira, André Luís B de Barros, Elaine A Leite
A long-circulating and pH-sensitive liposome containing paclitaxel (SpHL-PTX) was recently developed by our group. Once in an acidic environment, for example, tumors, these liposomes undergo destabilization, releasing the encapsulated drug. In this way, the aim of this study was to evaluate the molecular and supramolecular interactions between the lipid bilayer and PTX in similar biological environment conditions. High-sensitivity analyses of SpHL-PTX structures were obtained by the small-angle X-ray scattering technique combined with other techniques such as dynamic light scattering, asymmetric flow field-flow fractionation, transmission electron microscopy, and high-performance liquid chromatography...
May 22, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Ryohei Togashi, Hiroki Tanaka, Sakiko Nakamura, Hideo Yokota, Kota Tange, Yuta Nakai, Hiroki Yoshioka, Hideyoshi Harashima, Hidetaka Akita
Non-viral vectors are considered to be an attractive approach for gene delivery, since an artificial material is less immunogenic and oncogenic compared to a viral vector. We previously reported on the hepatic delivery of plasmid DNA (pDNA) by using lipid-like material (an SS-cleavable and pH-activated lipid-like material: ssPalm) which mounts two hydrophobic scaffolds, proton-accepting motifs (tertiary amines), and a cleavable unit (disulfide bonding). In the present study, we report on an advanced hepatic gene delivery system that uses a new type of ssPalm derivative: ssPalmE-Paz4-C2...
June 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Juan Song, Ran Wang, Zao Liu, Huashan Zhang
The influence of lecithin from egg yolk (LE) on calcium carbonate (CaCO3) biomineralization was investigated. In the present study, spherical CaCO3 particles were synthesized via coprecipitation in the presence of LE. LE multilamellar liposomes were first tuned by sonication to provide better control over the nucleation of CaCO3. Subsequently, monodisperse microspheres ~2 µm in size were generated by controlling the aggregation and growth of CaCO3 under appropriate concentrations of LE. In contrast to unstable vaterite, the microspheres generated in aqueous solution remained stable for at least 10 days without transforming into calcite, due to the strong interaction between the LE and calcium ions...
June 2018: Molecular Medicine Reports
Mengjia Zhao, Sang Hoon Lee, Jae Geun Song, Hyeon Young Kim, Hyo-Kyung Han
This study aimed to design the effective formulation of sorafenib (SF) to enhance the oral drug absorption. Three liposomal formulations of SF were prepared including uncoated liposome (SF-Lip), glycol chitosan-coated liposome (GC-SF-Lip), and Eudragit S100-glycol-chitosan coated liposome (SGC-SF-Lip). All formulations showed a narrow size distribution with a high encapsulation efficiency. Both GC-SF-Lip and SGC-SF-Lip exhibited good stability at acidic and neutral pHs without any significant drug leakage, while SF-Lip appeared to be unstable at pH 1...
June 10, 2018: International Journal of Pharmaceutics
Venkanna Muripiti, Hari Krishnareddy Rachamalla, Rajkumar Banerjee, Srilakshmi V Patri
Endosomal escape is one of the barriers for the efficient liposomal gene delivery. To address this and based on earlier encouraging results using tocopherol cationic lipids, we elaborated chemical modifications on tocopherol cationic lipids by introducing a novel hybrid pH sensitive linker "ether-β-hydroxy-triazole" between tocopherol, the anchoring moiety and the basic tris(2-hydroxy ethyl)quaternary ammonium head group (Lp2). As control lipids we designed two lipids (Lp1 and Lp3), one is with only the ether-β-hydroxy linker in between α-tocopherol and quaternary tris(2-hydroxyethyl)ammonium (Lp1) and the other is with the same novel hybrid linker i...
April 25, 2018: Organic & Biomolecular Chemistry
Vincenzo De Leo, Francesco Milano, Erminia Mancini, Roberto Comparelli, Livia Giotta, Angelo Nacci, Francesco Longobardi, Antonella Garbetta, Angela Agostiano, Lucia Catucci
The present study aimed to develop and optimize liposome formulation for the colonic delivery of biologically active compounds. A strategy to facilitate such targeting is to formulate liposomes with a polymer coating sensitive to the pH shifts in the gastrointestinal tract. To this end, liposomes encapsulating curcumin-chosen as the biologically active compound model-and coated with the pH-responsive polymer Eudragit S100 were prepared and characterized. Curcumin was encapsulated into small unilamellar vesicles (SUVs) by the micelle-to-vesicle transition method (MVT) in a simple and organic solvent-free way...
March 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yan Chen, Yao Cheng, Pengxuan Zhao, Shasha Zhang, Minsi Li, Chuanchuan He, Xiaojuan Zhang, Tan Yang, Ruicong Yan, Peng Ye, Xiang Ma, Guangya Xiang
Multidrug resistance to chemotherapeutic drugs is a major obstacle to breast cancer treatment. In this study, doxorubicin (DOX) and imatinib (IM) were co-loaded into folate receptor targeted (FR-targeted) pH-sensitive liposomes (denoted as FPL-DOX/IM) to fulfill intracellular acid-sensitive release and reverse drug resistance. FPL-DOX/IM could maintain stability in blood circulation with approximate diameters of 100 nm and rapidly release encapsulated drugs in tumor acidic microenvironment. Moreover, the IM in combination therapy could overcome chemoresistance associated with DOX effectively by inhibiting ABC transporter function and improving chemotherapy sensitivity...
May 5, 2018: International Journal of Pharmaceutics
Jiulong Zhang, Chunrong Yang, Shuang Pan, Menghao Shi, Jie Li, Haiyang Hu, Mingxi Qiao, Dawei Chen, Xiuli Zhao
Mitochondrial-targeting therapy was considered to be a promising approach for the efficient treatment of cancer while positive charge induced nonspecific cytotoxicity severely limits its application. To overcome this drawback, a novel mitochondria targeted conjugate triphenylphosphine-docetaxel (TD) has been synthesized successfully and incorporated it into liposomes (EPSLP/TD), which possessed excellent pH-sensitive characteristic, EphA 10 mediated active targetability as well as mitochondria-targeting capability...
November 2018: Drug Delivery
Animesh Pan, Subhash C Bhattacharya, Animesh K Rakshit, Satya P Moulik
Development of stable self-assembled nanostructures (especially vesicles and liposomes), and understanding their physicochemical behaviors in aqueous solution is a long-standing topic of interest in chemical and biochemical research. In this progressive area, we report for the first-time formation of mixed micelles (at pH 12), and vesicles of anionic bolaamphiphiles (dicarboxylic acids viz. [Formula: see text] , with moderate values of n 10, 11, 12, and 14) in combination with a cationic surfactant decyltrimethylammonium bromide (C10 TAB) in buffered aqueous medium at different pH (6...
May 15, 2018: Journal of Colloid and Interface Science
Xunan Zhang, Wei Zong, Hongmei Bi, Kunming Zhao, Thomas Fuhs, Ying Hu, Wenlong Cheng, Xiaojun Han
As promising drug delivery vehicles, previous investigations of liposomes as carriers are primarily focused on insertion and modification of lipid membrane interfaces. The utility of inner core seems to be overlooked. Herein, we developed PSLs containing aqueous two phase system (ATPS), and intriguingly discovered their hierarchical release under acidic stimuli. ATPS containing two polymers (poly(ethylene glycol) (PEG) and dextran) is homogeneous beyond phase transition temperature when producing ATPS-liposomes, and separated into PEG-rich phase and dextran-rich phase after cooling down to room temperature...
February 17, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Jinyuan Ma, Hongjie Wu, Yang Li, Zehua Liu, Guihua Liu, Yuxin Guo, Zhenqing Hou, Qingliang Zhao, Dengyue Chen, Xuan Zhu
PURPOSE: This work was intended to develop novel doxorubicin (DOX)/zinc (II) phthalocyanine (ZnPc) co-loaded mesoporous silica (MSNs)@ calcium phosphate (CaP)@PEGylated liposome nanoparticles (NPs) that could efficiently achieve collaborative anticancer therapy by the combination of photodynamic therapy (PDT) and chemotherapy. The interlayer of CaP could be utilized to achieve pH-triggered controllable drug release, promote the cellular uptake, and induce cell apoptosis to further enhance the anticancer effects...
February 8, 2018: Pharmaceutical Research
M G Simões, A Hugo, P Alves, P F Pérez, A Gómez-Zavaglia, P N Simões
Liposomes are exceptional carriers for therapeutic drug delivery. However, they generally suffer from poor cell penetration, low half-life in bloodstream and loss of functionality during storage. To overcome these problems some strategies can be applied, such as functionalization with polymers and the use of protective molecules during dehydration processes. This work reports a complete study about the stability, including freeze-drying in the presence of trehalose, storage and internalization into HEp-2 cells, of stable formulations of pH sensitive polymer-liposome complexes (PLC) composed of soybean lecithin and crosslinked/non-crosslinked poly(acrylic acid) with a cholesterol end-group (CHO-PAA)...
April 1, 2018: Colloids and Surfaces. B, Biointerfaces
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