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pH sensitive liposome

Zili Gu, Qingjie Wang, Yanbin Shi, Yi Huang, Jing Zhang, Xinke Zhang, Guimei Lin
Immunotherapy has exhibited enormous practice in the treatment of melanoma because of the intrinsic properties of tumor. Tumor can downmodulate immune function via multiple mechanisms such as immune checkpoint pathways. The PD-L1 monoclonal antibodies that block the PD1/PD-L1 pathway, which induced tumor cells to evade an immune attack, can delay tumor growth efficiently with inevitable disadvantages such as low selectivity and systemic toxicity. Nanomedicine is clearly an approach that holds tremendous potential for addressing the shortcomings and assisting delivery of drugs with proper biodistribution...
August 7, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Mala Sharma, Chitranshu Pandey, Neha Sharma, M A Kamal, Usman Sayeed, Salman Akhtar
BACKGROUND: Nanotechnology pictures a breakthrough in the domain of cancer therapy owing to its novel properties and functions. This technology is quite amendable as it allows the scientists to engineer drug nanoparticles of dimensions 10nm - 500nm permitting them to pass via leaky vasculature of tumorigenic microenvironment with higher specificity, reduced cytotoxicity and effective release without any after effects. The central part of the review zooms onto the role of nanoparticles and their targeted delivery for the cure of cancer...
July 20, 2018: Anti-cancer Agents in Medicinal Chemistry
Nikolaos Naziris, Natassa Pippa, Dimitris Stellas, Varvara Chrysostomou, Stergios Pispas, Costas Demetzos, Marcin Libera, Barbara Trzebicka
Chimeric/mixed stimuli-responsive nanocarriers are promising agents for therapeutic and diagnostic applications, as well as in the combinatorial field of theranostics. Herein, we designed chimeric nanosystems, composed of natural phospholipid and pH-sensitive amphiphilic diblock copolymer, in different molar ratios and assessed the polymer lyotropic effect on their properties. Initially, polymer-grafted bilayers were evaluated for their thermotropic behavior by thermal analysis. Chimeric liposomes were prepared through thin-film hydration and the obtained vesicles were studied by light scattering techniques, to measure their physicochemical characteristics and colloidal stability, as well as by imaging techniques, to elucidate their global and membrane morphology...
July 20, 2018: AAPS PharmSciTech
Siyam M Ansar, Wenlei Jiang, Thilak Mudalige
To understand the quality, efficacy, and safety of liposomal drugs, it is necessary to develop a robust and accurate method for the separation and the quantification of unencapsulated and liposome-associated drugs (or liposomal encapsulated drugs). Conventional methods involve separation of unencapsulated and liposome-associated drug using solid phase extraction and further drug quantification. This is a lengthy process, and sometimes solid phase extraction induces drug leakage from the liposomes causing erroneous results...
July 5, 2018: International Journal of Pharmaceutics
Manju Kanamala, Brian D Palmer, William R Wilson, Zimei Wu
To facilitate the development of PEG-cleavable pH-sensitive liposomes (CL-pPSL), this study aimed to fully characterize a new pH-sensitive polymer, PEGB -Hz-CHEMS. Polyethylene glycol (PEG) functionalised with 4-carboxybenzaldehyde (PEGB ) was linked to cholesteryl hemisuccinate (CHEMS) via an acid labile hydrazide-hydrazone hybrid bond (CONHNCH) to form PEGB -Hz-CHEMS. The polymer was post-inserted into DOPE/CHEMS liposomes to form CL-pPSL. A validated stability-indicating HPLC-UV method was developed with the aid of multiple linear regression for the mobile phase...
July 4, 2018: International Journal of Pharmaceutics
Yuqiong Xia, Mei Fang, Jingyu Dong, Chunzhong Xu, Zhen Liao, Pengbo Ning, Qi Zeng
Multidrug resistance of tumour cells is one of the most important hurdles in tumour chemotherapy. To overcome the multidrug resistance, we constructed a pH-sensitive liposome formulation (pHSL) by loading tariquidar (TQR) and DOX simultaneously in this work. The formulation showed high stability at pH 7.4 and excellent sensitivity at acidic pH, which facilitated the delivery of TQR and DOX into cells. Cellular experiments demonstrated that the pHSL/TQR/DOX 0.05 could almost restore the drug sensitivity of OVCAR8/ADR cells...
June 27, 2018: Colloids and Surfaces. B, Biointerfaces
Sijia Wang, Tong Wang, Junqi Zhang, Shouhong Xu, Honglai Liu
Antitumor peptides may potentially alleviate the problem of chemoresistance but do not yet target tumor cells and would be cytotoxic to normal cells. Here, we designed a pH-activated and thermosensitive lipopeptide (C6-Pep) containing a leucine zipper and an alkyl chain and assessed the ability of C6-Pep to kill cancer cells. Pep, the same sequence without the N-terminal hexanoic acid moiety, was generated as a less hydrophobic control. First, lipopeptide adsorption into lipid monolayers was studied using Langmuir-Blodgett and polarization modulation infrared reflection adsorption spectroscopy...
July 11, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
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)...
August 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...
August 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Xian Li, Xiudan Wang, Luping Sha, Da Wang, Wei Shi, Qinfu Zhao, Siling Wang
Thermochemotherapy 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 biocompatible nanocomposite thermosensitive mesoporous carbon nanoparticles (TSMCN) was prepared by covering a liposome on mesoporous carbon nanoparticles (MCN). The TSMCN had good photothermal efficiency and photostability. The doxorubicin (DOX)-loaded TSMCN (DOX/TSMCN) showed a slower release than the DOX-loaded MCN-COOH (DOX/MCN-COOH) both in simulated tumor environment and physiological environment...
June 13, 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
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