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Ph sensitive liposomes

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)...
January 23, 2018: Colloids and Surfaces. B, Biointerfaces
Yi-Ping Fang, Pei-Yu Hu, Yaw-Bin Huang
Introduction: Mitomycin C is an anticancer antibiotic agent that has the potential for broad-spectrum use against several cancers, including mammary cancers. Because its half-life is 17 min after a 30 mg intravenous bolus administration, the suitability of mitomycin C for wide use in the clinical setting is limited. Based on tumor pathophysiology, pH-sensitive liposomes could provide better tumor-targeted effects. The aim of this study was to investigate the possibility of diminishing the side effect of mitomycin C by using pH-sensitive liposomes...
2018: Drug Design, Development and Therapy
Daniel Calle, Paloma Ballesteros, Sebastián Cerdán
Clinical imaging modalities have reached a prominent role in medical diagnosis and patient management in the last decades. Different image methodologies as Positron Emission Tomography, Single Photon Emission Tomography, X-Rays, or Magnetic Resonance Imaging are in continuous evolution to satisfy the increasing demands of current medical diagnosis. Progress in these methodologies has been favored by the parallel development of increasingly more powerful contrast agents. These are molecules that enhance the intrinsic contrast of the images in the tissues where they accumulate, revealing noninvasively the presence of characteristic molecular targets or differential physiopathological microenvironments...
2018: Methods in Molecular Biology
Seiji Okazaki, Tadashi Iwasaki, Eiji Yuba, Shinobu Watarai
pH-Sensitive fusogenic polymer-modified (pH-sensitive) liposomes co-loaded with tumor model antigen, ovalbumin (OVA), and adjuvant, α-galactosylceramide (α-GalCer) were fabricated and administered subcutaneously into mice. The ability of pH-sensitive liposomes containing OVA and α-GalCer to stimulate cellular and humoral immune responses in vivo was compared with OVA-encapsulating pH-sensitive liposomes as well as with OVA alone. After immunization, significant OVA-specific antibodies were detected in the serum...
December 28, 2017: Journal of Veterinary Medical Science
Mahantesh Jadhav, Rahul S Kalhapure, Sanjeev Rambharose, Chunderika Mocktar, Sanil Singh, Tetsuya Kodama, Thirumala Govender
The acidic environment at bacterial infection sites is a potential external stimulus for targeted antibiotic delivery. This paper reports new biocompatible pH-sensitive lipids (PSLs) with three hydrocarbon tails, and a head group with a secondary amine and carboxylate function for site-specific nano delivery of vancomycin (VCM). PSLs formed stable liposomes with mean vesicle diameters and polydispersity indices between 99.38 ± 6.59 nm to 105.60 ± 5.38 nm and 0.161 ± 0.003 to 0.219 ± 0...
January 2, 2018: Chemistry and Physics of Lipids
Jiongxi Lei, Shuangchen Cong, Maoyuan Song, Wenxi Zhang, Guanghua Peng, Xinru Li, Yan Liu
CONTEXT: Long-circulation (PEGLip), pH-sensitive (PEOzLip), and active targeted liposomes (PEG-TATLip)-loading doxorubicin (DOX) and harmine (HM) were prepared. Their physicochemical properties and antitumor effect were investigated. OBJECTIVES: The aims of the present study were to evaluate synergistic antitumor efficacy. MATERIALS AND METHODS: Liposomes were prepared by using thin-film dispersion, active drug-loading and target post-insertion method...
January 9, 2018: Drug Development and Industrial Pharmacy
Parvin Zamani, Amir Abbas Momtazi-Borojeni, Maryam Ebrahimi Nik, Reza Kazemi Oskuee, Amirhossein Sahebkar
Cancer immunotherapy is one of the commonly used methods in the treatment of cancer. The aim of this approach is to strengthen or restore immune function for effective diagnosis of aberrant cells antigens. For this reason, cancer specific peptides or proteins are used as antigens to induce an immune response capable of removing cancer cells. Liposomal formulations are an important carrier system frequently used for delivery of antigen because the specific properties of this component such as lipid composition, charge, size, encapsulation of antigens or adjuvants can be changed...
December 7, 2017: Journal of Cellular Physiology
Maiko Miyazaki, Eiji Yuba, Hiroshi Hayashi, Atsushi Harada, Kenji Kono
For the enhancement of therapeutic effects and reduction of side effects derived from anticancer drugs in cancer chemotherapy, it is imperative to develop drug delivery systems with cancer-specificity and controlled release function inside cancer cells. pH-Sensitive liposomes are useful as an intracellular drug delivery system because of their abilities to transfer their contents into the cell interior through fusion or destabilization of endosome, which has weakly acidic environment. We earlier reported liposomes modified with various types of pH-sensitive polymers based on synthetic polymers and biopolymers as vehicles for intracellular drug delivery systems...
November 28, 2017: Bioconjugate Chemistry
Yuan Ding, Wei Cui, Dan Sun, Gui-Ling Wang, Yu Hei, Shuai Meng, Jian-Hua Chen, Ying Xie, Zhi-Qiang Wang
In vivo evaluation of drug delivery vectors is essential for clinical translation. In BALB/c nude mice bearing human breast cancer tumors, we investigated the biocompatibility, pharmacokinetics, and pharmacodynamics of doxorubicin (DOX)-loaded novel cell-penetrating peptide (CPP)-modified pH-sensitive liposomes (CPPL) (referred to as CPPL(DOX)) with an optimal CPP density of 4%. In CPPL, a polyethylene glycol (PEG) derivative formed by conjugating PEG with stearate via acid-degradable hydrazone bond (PEG2000-Hz-stearate) was inserted into the surface of liposomes, and CPP was directly attached to liposome surfaces via coupling with stearate to simultaneously achieve long circulation time in blood and improve the selectivity and efficacy of CPP for tumor targeting...
2017: Drug Design, Development and Therapy
Yu Zheng, Xin Liu, Nataliya M Samoshina, Vyacheslav V Samoshin, Andreas H Franz, Xin Guo
Recently developed lipids with the trans-2-aminocyclohexanol (TACH) moiety represent unique pH-sensitive conformational switches ("flipids") that can trigger the membrane of liposome-based drug delivery systems at lowered pH as seen in many pathological scenarios. A library of flipids with various TACH-based headgroups and hydrocarbon tails were designed, prepared, and characterized to systematically elucidate the relationship between their chemical structures and their ability to form and to trigger liposomes...
October 27, 2017: Chemistry and Physics of Lipids
Huachao Chen, Yurong Wang, Yongrong Yao, Shenglin Qiao, Hao Wang, Ninghua Tan
A programmed drug delivery system that can achieve sequential release of multiple therapeutics under different stimulus holds great promise to enhance the treatment efficacy and overcome multi-drug resistance (MDR) in tumor. Herein, multi-organelle-targeted and pH/ cytochrome c (Cyt c) dual-responsive nanoparticles were designed for combination therapy on resistant tumor. In this system (designated DGLipo NPs), doxorubicin (Dox) was intercalated into the DNA duplex containing a Cyt c aptamer, which subsequently loaded in the dendrigraftpoly-L-lysines (DGL) cores of DGLipo NPs, while cyclopeptide RA-V was doped into the pH-sensitive liposomal shells...
2017: Theranostics
Mohadeseh Hashemi, Meisam Omidi, Bharadwaj Muralidharan, Lobat Tayebi, Matthew J Herpin, Mohammad Ali Mohagheghi, Javad Mohammadi, Hugh D C Smyth, Thomas E Milner
Stimuli responsive polyelectrolyte nanoparticles have been developed for chemo-photothermal destruction of breast cancer cells. This novel system, called layer by layer Lipo-graph (LBL Lipo-graph), is composed of alternate layers of graphene oxide (GO) and graphene oxide conjugated poly (l-lysine) (GO-PLL) deposited on cationic liposomes encapsulating doxorubicin. Various concentrations of GO and GO-PLL were examined and the optimal LBL Lipo-graph was found to have a particle size of 267.9 ± 13 nm, zeta potential of +43...
January 2018: Acta Biomaterialia
Liziane O F Monteiro, Renata S Fernandes, Caroline M R Oda, Sávia C Lopes, Danyelle M Townsend, Valbert N Cardoso, Mônica C Oliveira, Elaine A Leite, Domenico Rubello, André L B de Barros
A range of antitumor agents for cancer treatment is available; however, they show low specificity, which often limit their use. Recently, we have reported the preparation of folate-coated long-circulating and pH-sensitive liposomes (SpHL-folate-PTX) loaded with paclitaxel (PTX), an effective drug for the treatment of solid tumors, including breast cancer. The purpose of this study was to prepare and characterize SpHL-PTX and SpHL-folate-PTX radiolabeled with technetium-99m ((99m)Tc). Biodistribution studies and scintigraphic images were performed after intravenous administration of (99m)Tc-PTX, (99m)Tc-SpHL-PTX and (99m)Tc-SpHL-folate-PTX into healthy and tumor-bearing mice...
October 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ruixue Bai, Xueqing Deng, Qiong Wu, Xiaomian Cao, Tiantian Ye, Shujun Wang
Main challenges of the clinical use of 7-ethyl-10-hydroxycamptothecin (SN-38) are its facile transition between the active lactone form (SN-38A) and the inactive carboxylate form (SN-38I) under physiological conditions and its low solubility. The purpose of this study was to develop a thermo-sensitive hydrogel system with acidic SN-38 liposomes (SN-38-Lip-Gel) for local chemotherapy to solve these problems and to evaluate its antitumor activity and tissue distribution in tumor-bearing mice. A study of structural conversion between SN-38I and SN-38A under various pH conditions indicated that acidic solution could inhibit the conversion...
October 11, 2017: Pharmaceutical Development and Technology
Atefeh Arab, Javad Behravan, Atefeh Razazan, Zahra Gholizadeh, Amin Reza Nikpoor, Nastaran Barati, Fatemeh Mosaffa, Ali Badiee, Mahmoud Reza Jaafari
E75 (HER-2/neu-369-377), is an immunogenic peptide which is highly expressed in breast cancer patients. The purpose of this study was to develop an effective vaccine delivery/adjuvant system by attachment of this peptide to the surface of liposomes consisting of phospholipids including DSPC and DSPG with high transition temperature (Tm) and DOPE (a pH-sensitive lipid for cytosolic antigen delivery) to improve anti-tumor immune activity against the E75 peptide. For this purpose, the E75 peptide was incorporated into liposomes consisting of DSPC/DSPG/Chol/DOPE (15/2/3/5 molar ratio) through conjugation with maleimide-PEG2000-DSPE...
October 3, 2017: Journal of Drug Targeting
Zili Gu, Minglu Chang, Yang Fan, Yanbin Shi, Guimei Lin
As current tumor chemotherapy faces many challenges, it is important to develop drug delivery systems with increased tumor-targeting ability, enhanced therapeutic effects and reduced side effects. In this study, a pH-sensitive liposome was constructed containing CHEMS-anchored PEG2000 for extended circulation and NGR peptide as the targeting moiety. The NGR-modified docetaxel-loaded pH-sensitive extended-circulation liposomes (DTX/NGR-PLL) prepared possess suitable physiochemical properties, including particle size of approximately 200nm, drug encapsulation efficiency of approximately 70%, and pH-sensitive drug release properties...
September 23, 2017: Colloids and Surfaces. B, Biointerfaces
Xiao-Ru Shao, Xue-Qin Wei, Shu Zhang, Na Fu, Yun-Feng Lin, Xiao-Xiao Cai, Qiang Peng
Liposome is a promising carrier system for delivering bioactive molecules. However, the successful delivery of pH-sensitive molecules is still limited by the intrinsic instability of payloads in physiological environment. Herein, we developed a special liposome system that possesses an acidic micro-environment in the internal aqueous chamber to improve the chemical stability of pH-sensitive payloads. Curcumin-loaded liposomes (Cur-LPs) with varied internal pH values (pH 2.5, 5.0, or 7.4) were prepared. These Cur-LPs have similar particle size of 300 nm, comparable physical stabilities and analogous in vitro release profiles...
August 23, 2017: Nanoscale Research Letters
Yotam Navon, Harisoa Radavidson, Jean-Luc Putaux, Bruno Jean, Laurent Heux
The interaction of 1,2 dioleolyl-sn-glycero-3-phosphatidylcholine (DOPC) vesicles with cellulose nanocrystals (CNCs) using several complementary techniques. Dynamic light scattering, zeta-potential, cryo-transmission electron microscopy and isothermal titration calorimetry (ITC) analyses confirmed the formation of pH-dependent CNC-liposome complexes. ITC was used to characterize the thermodynamic properties of this interaction. Positive values of enthalpy were found at pH lower than 5 where the charge sign of the constituents was opposite...
August 29, 2017: Biomacromolecules
Kenneth T Lewis, Akshata R Naik, Suvra S Laha, Sunxi Wang, Guangzhao Mao, Eric Kuhn, Bhanu P Jena
A wide range of cellular activities including protein folding and cell secretion, such as neurotransmission or insulin release, are all governed by intracellular pH homeostasis, underscoring the importance of pH on critical life processes. Nano- scale pH measurements of cells and biomolecules therefore hold great promise in understanding a plethora of cellular functions, in addition to disease detection and therapy. In the current study, a novel approach using cadmium telluride quantum dots (CdTeQDs) as pH sensors, combined with fluorescent imaging, spectrofluorimetry, atomic force microscopy (AFM), and Western blot analysis, enabled the study of intracellular pH dynamics at 1 milli-pH sensitivity and 80nm pixel resolution, during insulin secretion...
August 2, 2017: Seminars in Cell & Developmental Biology
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