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Ph sensitive liposomes

Azadeh Kheirolomoom, Elizabeth S Ingham, Joel Commisso, Neveen Abushaban, Katherine W Ferrara
We previously developed a pH-responsive copper-doxorubicin (CuDox) cargo in lysolipid-based temperature-sensitive liposomes (LTSLs). The CuDox complex is released from the particle by elevated temperature; however, full release of doxorubicin from CuDox requires a reduced pH, such as that expected in lysosomes. The primary goal of this study is to evaluate the cellular uptake and intracellular trafficking of the drug-metal complex in comparison with intact liposomes and free drug. We found that the CuDox complex was efficiently internalized by mammary carcinoma cells after release from LTSLs...
October 13, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Yuta Yoshizaki, Eiji Yuba, Toshihiro Komatsu, Keiko Udaka, Atsushi Harada, Kenji Kono
To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and l-dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG) and were loaded with antigenic peptides derived from ovalbumin (OVA) OVA-I (SIINFEKL), and OVA-II (PSISQAVHAAHAEINEAPβA), which bind, respectively, to major histocompatibility complex (MHC) class I and class II molecules on dendritic cell (DCs)...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Charlotte Toulouse, Björn Claussen, Valentin Muras, Günter Fritz, Julia Steuber
The Na+-translocating NADH:quinone oxidoreductase (NQR) is the entry site for electrons into the respiratory chain of Vibrio cholerae, the causative agent of cholera disease. NQR couples the electron transfer from NADH to ubiquinone to the translocation of sodium ions across the membrane. We investigated the pH dependence of electron transfer and generation of a transmembrane voltage (ΔΨ) by NQR reconstituted in liposomes with Na+ or Li+ as coupling cation. ΔΨ formation was followed with the voltage-sensitive dye oxonol...
September 17, 2016: Biological Chemistry
Ana Luiza Chaves Maia, Christian Fernandes, Cynthia Nara Pereira de Oliveira, Claudia Salviano Teixeira, Mariana Silva Oliveira, Daniel Cristian Soares, Gilson Andrade Ramaldes
The aim of this study was develop, characterize and assess the cytotoxic activity of pH-sensitive (pHL-Gd), stealth pH-sensitive (SpHL-Gd), and conventional (convL-Gd) liposomes containing gadodiamide (Gd-DTPA-BMA). Formulations were prepared by reverse-phase evaporation method and their physicochemical properties were evaluated by means of particle size, zeta potential, and Gd-DTPA- BMA entrapment. SpHL-Gd was considered the most promising liposome, since it combines stealth and fusogenic characteristics that can contribute for higher therapeutic efficiency...
September 6, 2016: Current Drug Delivery
Luisa Giansanti, Alessandro Mauceri, Luciano Galantini, Barbara Altieri, Antonella Piozzi, Giovanna Mancini
The inclusion of pH-sensitive components in liposome formulations can allow a more controlled and efficient release in response to low pH typical of some pathological tissues and/or subcellular compartments. On the other hand decorating the surface of liposomes with sugar moieties attributes to lipid vesicles specificity toward lectins, sugar-binding proteins overexpressed in many tumor tissues. A novel multifunctional pH-sensitive glucosylated amphiphile was synthesized and characterized as pure aggregate component and in mixtures with a natural phospholipid...
September 4, 2016: Chemistry and Physics of Lipids
Xinlong Zang, Huaiwei Ding, Xiufeng Zhao, Xiaowei Li, Zhouqi Du, Haiyang Hu, Mingxi Qiao, Dawei Chen, Yuihui Deng, Xiuli Zhao
Therapeutic delivery of small interfering RNA (siRNA) is a major challenge that limits its potential clinical application. Here, a pH-sensitive cholesterol-Schiff base-polyethylene glycol (Chol-SIB-PEG)-modified cationic liposome-siRNA complex, conjugated with the recombinant humanized anti-EphA10 antibody (Eph), was developed as an efficient nonviral siRNA delivery system. Chol-SIB-PEG was successfully synthesized and confirmed with FTIR and (1)H-NMR. An Eph-PEG-SIB-Chol-modified liposome-siRNA complex (EPSLR) was prepared and characterized by size, zeta potential, gel retardation, and encapsulation efficiency...
2016: International Journal of Nanomedicine
Diêgo Dos Santos Ferreira, Samilla Dornelas Faria, Sávia Caldeira de Araújo Lopes, Cláudia Salviano Teixeira, Angelo Malachias, Rogério Magalhães-Paniago, José Dias de Souza Filho, Bruno Luis de Jesus Pinto Oliveira, Alexander Ramos Guimarães, Peter Caravan, Lucas Antônio Miranda Ferreira, Ricardo José Alves, Mônica Cristina Oliveira
BACKGROUND: Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges. PURPOSE: To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX) in an acidic environment for future application as a tool for treatment of bone metastases...
2016: International Journal of Nanomedicine
Nikolaos Naziris, Natassa Pippa, Anastasia Meristoudi, Stergios Pispas, Costas Demetzos
The application of stimuli-responsive medical practices has emerged, in which pH-sensitive liposomes figure prominently. This study investigates the impact of the incorporation of different amounts of pH-sensitive polymer, C12H25-PAA (poly(acrylic acid) with a hydrophobic end group) in L-α-phosphatidylcholine, hydrogenated (Soy) (HSPC) phospholipidic bilayers, with respect to biomimicry and functionality. PAA is a poly(carboxylic acid) molecule, classified as a pH-sensitive polymer, whose pH-sensitivity is attributed to its regulative -COOH groups, which are protonated under acidic pH (pKa∼4...
August 25, 2016: Journal of Liposome Research
Tiantian Zuo, Yuanyuan Guan, Minglu Chang, Fang Zhang, Shanshan Lu, Ting Wei, Wei Shao, Guimei Lin
The goal of this research was to formulate dual-targeting liposomes (RGD/DTX-PSL) that can selectively release loaded contents in a low pH level environment and to actively target to the tumor using liposomes that had surface arginine-glycine-aspartic (RGD) tripeptides. We investigated whether RGD/DTX-PSL could serve as an effective tumor-targeted nanoparticle that is capable of suppressing tumor growth. The results suggest that DTX is released from liposomes faster at pH 5.0 than pH 7.4, demonstrating their pH sensitivity...
November 1, 2016: Colloids and Surfaces. B, Biointerfaces
Marian Vila-Caballer, Gaia Codolo, Fabio Munari, Alessio Malfanti, Matteo Fassan, Massimo Rugge, Anna Balasso, Marina de Bernard, Stefano Salmaso
Stealth pH-responsive liposomes for the delivery of therapeutic proteins to the bladder epithelium were prepared using methoxy-poly(ethylene glycol)5kDa-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG5kDa-DSPE) and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (stearoyl-PEG-polySDM), which possesses an apparent pKa of 7.2. Liposomes of 0.2:0.6:100, 0.5:1.5:100 and 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/(soybean phosphatidylcholine+cholesterol) molar ratios were loaded with bovine serum albumin (BSA) as a protein model...
September 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Wei-Yi Gong, Ramy E Abdelhamid, Carolina S Carvalho, Kathleen A Sluka
UNLABELLED: Macrophages play a role in innate immunity within the body, are located in muscle tissue, and can release inflammatory cytokines that sensitize local nociceptors. In this study we investigate the role of resident macrophages in the noninflammatory muscle pain model induced by 2 pH 4.0 preservative-free sterile saline (pH 4.0) injections 5 days apart in the gastrocnemius muscle. We showed that injecting 2 pH 4.0 injections into the gastrocnemius muscle increased the number of local muscle macrophages, and depleting muscle macrophages with clodronate liposomes before acid injections attenuated the hyperalgesia produced by this model...
October 2016: Journal of Pain: Official Journal of the American Pain Society
Sören Draffehn, Jenny Eichhorst, Burkhard Wiesner, Michael U Kumke
Encapsulation of diagnostic and therapeutic compounds in transporters improves their delivery to the point of need. An even more efficient treatment of diseases can be achieved using carriers with targeting or protecting moieties. In the present work, we investigated micellar and liposomal nanocarriers modified with fluorescein, peptides, and polymers that are covalently bound to fatty acids or phospholipids to ensure a self-driven incorporation into the micelles or liposomes. First, we characterized the photophysics of the fluorescent probes in the absence and in the presence of nanocarriers...
July 12, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Yeon Su Choi, Dong Youl Cho, Hye-Kyung Lee, Jung-Kyo Cho, Don Haeng Lee, You Han Bae, Ja-Kyeong Lee, Han Chang Kang
UNLABELLED: Nucleotides (NTs) (e.g., adenosine triphosphate) are very important molecules in the body. They generate bioenergy through phosphate group release, are involved in various biological processes, and are used to treat various diseases that involve energy depletion. However, their highly anionic characteristics might limit delivery of exogenous NTs into the cell, which is required to realize their functions as bioenergy sources. In this study, ionic complexation between Ca(2+) and NT phosphates was used to form Ca(2+)/NT nanocomplexes (NCs), and branched polyethyleneimine (bPEI1...
September 1, 2016: Acta Biomaterialia
Ofonime Udofot, Kevin Affram, Taylor Smith, Bulumko Tshabe, Sunil Krishnan, Mandip Sachdeva, Edward Agyare
The objective of the study was to investigate the pharmacokinetics and efficacy of 5-FU entrapped pH-sensitive liposomal nanoparticles with surface-modified anti-epidermal growth factor receptor (EGFR) antibody (pHLNps-5-FU) delivery system. Cytotoxicity of 5-FU and pHLNps-5-FU was determined in vitro against HCT-116 cells. The biodistribution and pharmacokinetic parameters of the administered 5-FU and pHLNps-5-FU as well as efficacy of 5-FU and pHLNps-5-FU were determined in HCT-116 subcutaneous mouse model...
2016: Journal of Nature and Science
Wei Zong, Ying Hu, Yingchun Su, Nan Luo, Xunan Zhang, Qingchuan Li, Xiaojun Han
Stimuli-responsive drug carriers are considered to play important roles in chemotherapy. We fabricated pH-sensitive polydopamine-protected liposomes (liposome@PDA) drug delivery systems, which were characterised with microscope, scanning electron microscope (SEM), UV-vis spectrometer and Fourier transform infrared (FTIR) technieques. The typical chemotherapeutic agent, 5-fluorouracil (5-FU), was loaded into liposome@PDA capsules. The maximum release percentages of 5-FU are 3.2%, 29.5%, 52.7%, 76.7% in the solution with pH 7...
May 2016: Journal of Microencapsulation
Juliana O Silva, Renata S Fernandes, Sávia C A Lopes, Valbert N Cardoso, Elaine A Leite, Geovanni D Cassali, Maria Cristina Marzola, Domenico Rubello, Monica C Oliveira, Andre Luis Branco de Barros
PURPOSE: Therapeutic agents used in chemotherapy have low specificity leading to undesired severe side effects. Hence, the development of drug delivery systems that improve drug specificity, such as liposome moieties, is an alternative to overcome chemotherapy limitations and increase antitumor efficacy. In this study, the biodistribution profile evaluation of pH-sensitive long-circulating liposomes (SpHL) containing [(99m)Tc]DOX in 4T1 tumor-bearing BALB/c mice is described. PROCEDURES: [(99m)Tc]DOX was radiolabeled by direct method...
May 12, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Shoko Itakura, Susumu Hama, Ryo Matsui, Kentaro Kogure
Condensing siRNA with cationic polymers is a major strategy used in the development of siRNA carriers that can avoid degradation by nucleases and achieve effective delivery of siRNA into the cytoplasm. However, ineffective release of siRNA from such condensed forms into the cytoplasm is a limiting step for induction of RNAi effects, and can be attributed to tight condensation of siRNA with the cationic polymers, due to potent electrostatic interactions. Here, we report that siRNA condensed with a slightly acidic pH-sensitive peptide (SAPSP), whose total charge is inverted from positive to negative in response to cytoplasmic pH, is effectively released via electrostatic repulsion of siRNA with negatively charged SAPSP at cytoplasmic pH (7...
May 19, 2016: Nanoscale
Talita Guieiro Ribeiro Rocha, Sávia Caldeira de Araújo Lopes, Geovani Dantas Cassali, Ênio Ferreira, Emerson Soares Veloso, Elaine Amaral Leite, Fernão Castro Braga, Lucas Antônio Miranda Ferreira, Daniel Balvay, Anikitos Garofalakis, Mônica Cristina Oliveira, Bertrand Tavitian
Background Ursolic acid (UA) is a triterpene found in different plant species, possessing antitumor activity, which may be a result of its antiangiogenic effect. However, UA has low water solubility, which limits its use because the bioavailability is impaired. To overcome this inconvenience, we developed long-circulating and pH-sensitive liposomes containing ursolic acid (SpHL-UA). We investigated the antiangiogenic effect of free UA and SpHL-UA in murine brain cancer and human breast tumor models by means of determination of the relative tumor volume, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and histopathological analysis...
April 29, 2016: Integrative Cancer Therapies
Yang Wang, Kairong Shi, Li Zhang, Guanlian Hu, Jingyu Wan, Jiajing Tang, Sheng Yin, Jiandong Duan, Ming Qin, Neng Wang, Dandan Xie, Xinle Gao, Huile Gao, Zhirong Zhang, Qin He
Hydroxychloroquine (HCQ) inhibits autophagy and therefore can sensitize some cancer cells to chemotherapy, but the high doses required limit its clinical use. Here we show that loading HCQ into liposomes (HCQ/Lip) decorated with a pH-sensitive TH-RGD targeting peptide (HCQ/Lip-TR) can concentrate HCQ in B16F10 tumor cells and lysosomes. HCQ/Lip-TR was efficiently internalized as a result of its ability to bind ITGAV-ITGB3/integrin αvβ3 receptors highly expressed on the tumor cell surface and to undergo charge reversal from anionic at pH 7...
June 2, 2016: Autophagy
Yumeng Wei, Chao Pi, Gang Yang, Xiaoming Xiong, Yongshu Lan, Hongru Yang, Yang Zhou, Yun Ye, Yonggen Zou, Wenwu Zheng, Ling Zhao
A simple and sensitive LC-UV method to investigate the pharmacokinetics and biodistribution pattern of baicalin in rabbits was established and validated. Baicalin and the internal standard, rutin, were extracted from biosamples using acetonitrile as protein precipitation after pretreated with ammonium acetate buffer (pH 3.5; 1 M) to obtain a pure chromatographic peak and high extraction recovery. Chromatographic separation was achieved on a reverse-phase C18 column with a gradient elution at flow rate of 1...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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