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https://www.readbyqxmd.com/read/28934610/chitosan-lipid-nanoparticles-cs-lnps-application-to-sirna-delivery
#1
Özgül Tezgel, Anna Szarpak-Jankowska, Amandine Arnould, Rachel Auzély-Velty, Isabelle Texier
To benefit from the biocompatibility of lipid nanoparticles associated with the transfection ability of chitosan, small chitosan lipid nanoparticles (CS-LNPs) dedicated to SiRNA delivery were formulated by an easy-to-implement one-step process. Formulations of CS-LNPs (lipid core stabilized by a shell comprising phospholipids/cationic lipids and hydrophobically modified chitosan) were optimized for their physico-chemical properties (size, zeta potential, colloidal stability) according to their shell composition...
September 11, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28921566/pegylation-of-cationic-liposomes-encapsulating-soluble-leishmania-antigens-sla-reduces-the-adjuvant-efficacy-of-liposomes-in-murine-model
#2
Hadi Naseri, Faezeh Eskandari, Mahmoud Reza Jaafari, Ali Khamesipour, Azam Abbasi, Ali Badiee
Although there have been several attempts to develop a vaccine against leishmaniasis; no vaccine in human has been developed yet. Liposomes consisting of 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) encapsulating soluble Leishmania antigens (SLA) enhance protective immunity of SLA against L. major infection in mice. However, they immobilized at the injection site because of their positive charge. To overcome the problem, shielding the surface charge with polyethylene glycol (PEGylation) was chosen in this study...
September 16, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28915590/combination-of-desi2-and-ip10-gene-therapy-significantly-improves-therapeutic-efficacy-against-murine-carcinoma
#3
Chao Lin, HuaYing Yan, Jun Yang, Lei Li, Mei Tang, Xinyu Zhao, Chunlai Nie, Na Luo, Yuquan Wei, Zhu Yuan
DESI2 (also known as PNAS-4) is a novel pro-apoptotic gene activated during the early response to DNA damage. We previously reported that overexpression of DESI2 induces S phase arrest and apoptosis by activating checkpoint kinases. The present study was designed to test whether combination of DESI2 and IP10 could improve the therapy efficacy in vitro and in vivo. The recombinant plasmid co-expressing DESI2 and IP10 was encapsulated with DOTAP/Cholesterol nanoparticle. Immunocompetent mice bearing CT26 colon carcinoma and LL2 lung cancer were treated with the complex...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28889081/distinct-solubility-and-cytotoxicity-regimes-of-paclitaxel-loaded-cationic-liposomes-at-low-and-high-drug-content-revealed-by-kinetic-phase-behavior-and-cancer-cell-viability-studies
#4
Victoria M Steffes, Meena M Murali, Yoonsang Park, Bretton J Fletcher, Kai K Ewert, Cyrus R Safinya
Lipid-based particles are used worldwide in clinical trials as carriers of hydrophobic paclitaxel (PTXL) for cancer chemotherapy, albeit with little improvement over the standard-of-care. Improving efficacy requires an understanding of intramembrane interactions between PTXL and lipids to enhance PTXL solubilization and suppress PTXL phase separation into crystals. We studied the solubility of PTXL in cationic liposomes (CLs) composed of positively charged 2,3-dioleyloxypropyltrimethylammonium chloride (DOTAP) and neutral 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) as a function of PTXL membrane content and its relation to efficacy...
November 2017: Biomaterials
https://www.readbyqxmd.com/read/28884630/fetal-and-placental-dna-stimulation-of-tlr9-a-mechanism-possibly-contributing-to-the-pro-inflammatory-events-during-parturition
#5
Ilona Telefus Goldfarb, Sharareh Adeli, Tucker Berk, Mark Phillippe
INTRODUCTION: While there is evidence for a relationship between cell-free fetal DNA (cffDNA) and parturition, questions remain regarding whether cffDNA could trigger a pro-inflammatory response on the pathway to parturition. We hypothesized that placental and/or fetal DNA stimulates toll-like receptor 9 (TLR9) leading to secretion of pro-inflammatory cytokines by macrophage cells. METHODS: Four in vitro DNA stimulation studies were performed using RAW 264.7 mouse peritoneal macrophage cells incubated in media containing the following DNA particles: an oligodeoxynucleotide (ODN2395), intact genomic DNA (from mouse placentas, fetuses and adult liver), mouse DNA complexed with DOTAP (a cationic liposome forming compound), and telomere-depleted mouse DNA...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28866132/combining-r-dotap-and-a-particulate-antigen-delivery-platform-to-trigger-dendritic-cell-activation-formulation-development-and-in-vitro-interaction-studies
#6
Markus Riehl, Meike Harms, Andrea Hanefeld, Renato B Baleeiro, Peter Walden, Karsten Mäder
The utilization of the cationic lipid R-DOTAP as immune cell stimulant (e.g. its stimulating effects on immature dendritic cells) and correspondingly as possible adjuvant for vaccination is well known. Likewise, it is described in literature that solid polymer particles loaded with antigens can be size-tailored in a manner to be suitable for phagocytosis by antigen presenting cells. The effects of DOTAP-microparticle combinations, however, are not well understood. This study aimed therefore to explore the potential of R-DOTAP stabilized microparticles (MP) to act as a carrier platform for antigens e...
September 1, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28762497/t-cell-dependent-antigen-adjuvanted-with-dotap-cpg-b-but-not-dotap-cpg-a-induces-robust-germinal-center-responses-and-high-affinity-antibodies-in-mice
#7
Munir Akkaya, Billur Akkaya, Patrick W Sheehan, Pietro Miozzo, Mirna Pena, Chen-Feng Qi, Javier Manzella-Lapeira, Silvia Bolland, Susan K Pierce
The development of vaccines for infectious diseases for which we currently have none, including HIV, will likely require the use of adjuvants that strongly promote germinal center responses and somatic hypermutation to produce broadly neutralizing antibodies. Here we compared the outcome of immunization with the T-cell dependent antigen, NP-conjugated to chicken gamma globulin (NP-CGG) adjuvanted with the toll-like receptor 9 (TLR9) ligands, CpG-A or CpG-B, alone or conjugated with the cationic lipid carrier, DOTAP...
August 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28762066/zeta-potential-a-case-study-of-cationic-anionic-and-neutral-liposomes
#8
Mackensie C Smith, Rachael M Crist, Jeffrey D Clogston, Scott E McNeil
Zeta potential is often used to approximate a nanoparticle's surface charge, i.e., cationic, anionic, or neutral character, and has become a standard characterization technique to evaluate nanoparticle surfaces. While useful, zeta potential values provide only very general conclusions about surface charge character. Without a thorough understanding of the measurement parameters and limitations of the technique, these values can become meaningless. This case study attempts to explore the sensitivity of zeta potential measurement using specifically formulated cationic, anionic, and neutral liposomes...
July 31, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28756280/engineering-of-small-interfering-rna-loaded-lipidoid-poly-dl-lactic-co-glycolic-acid-hybrid-nanoparticles-for-highly-efficient-and-safe-gene-silencing-a-quality-by-design-based-approach
#9
Kaushik Thanki, Xianghui Zeng, Sarah Justesen, Sarah Tejlmann, Emily Falkenberg, Elize Van Driessche, Hanne Mørck Nielsen, Henrik Franzyk, Camilla Foged
Safety and efficacy of therapeutics based on RNA interference, e.g., small interfering RNA (siRNA), are dependent on the optimal engineering of the delivery technology, which is used for intracellular delivery of siRNA to the cytosol of target cells. We investigated the hypothesis that commonly used and poorly tolerated cationic lipids might be replaced with more efficacious and safe lipidoids as the lipid component of siRNA-loaded lipid-polymer hybrid nanoparticles (LPNs) for achieving more efficient gene silencing at lower and safer doses...
July 26, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28736158/nanoliposomes-carrying-her2-neu-derived-peptide-ae36-with-cpg-odn-exhibit-therapeutic-and-prophylactic-activities-in-a-mice-tubo-model-of-breast-cancer
#10
Nastaran Barati, Amin Reza Nikpoor, Atefeh Razazan, Fatemeh Mosaffa, Ali Badiee, Atefeh Arab, Zahra Gholizadeh, Javad Behravan, Mahmoud Reza Jaafari
This study was designed to prepare and characterize nanoliposomal vaccine formulation encapsulating AE36 HER2/neu-derived peptide with or without CpG and evaluate the immunologic and therapeutic responses of that in BALB/c mice model of Her2 overexpressing breast cancer. AE36 was encapsulated in liposomes composed of DOTAP, DOPE and Cholesterol (DDC) or DD with. The formulations could induce both CD8+ and CD4+ responses and stimulate production of cytokines which was detected by Enzyme-linked immunospot assay (ELISpot) kits, cytotoxicity test and intracellular cytokine assay by flow cytometry...
July 21, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28729400/vessel-targeted-chemophototherapy-with-cationic-porphyrin-phospholipid-liposomes
#11
Dandan Luo, Jumin Geng, Nasi Li, Kevin A Carter, Shuai Shao, G Ekin Atilla-Gokcumen, Jonathan F Lovell
Cationic liposomes have been used for targeted drug delivery to tumor blood vessels, via mechanisms that are not fully elucidated. Doxorubicin (Dox)-loaded liposomes were prepared that incorporate a cationic lipid; 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), along with a small amount of porphyrin-phospholipid (PoP). Near infrared (NIR) light induced release of entrapped Dox via PoP-mediated DOTAP photo-oxidation. The formulation was optimized to enable extremely rapid NIR light-triggered Dox release (i...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28680130/surface-chemistry-for-cytosolic-gene-delivery-and-photothermal-transgene-expression-by-gold-nanorods
#12
Hirotaka Nakatsuji, Kelly Kawabata Galbraith, Junko Kurisu, Hiroshi Imahori, Tatsuya Murakami, Mineko Kengaku
Light-inducible gene regulation has great potential for remote and noninvasive control of the fate and function of target cells. One method to achieve such control is delivery of heat shock protein (HSP) promoter-driven protein expression vectors and photothermal heaters into the cells, followed by activation by illumination. In this study, we show that gold nanorods (AuNRs) functionalized with two conventional lipids, oleate and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), are capable of efficient transfection and quick photoactivation of the HSP promoter...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28669809/functional-nanosome-for-enhanced-mitochondria-targeted-gene-delivery-and-expression
#13
Yoonhee Bae, Min Kyo Jung, Su Jeong Song, Eric S Green, Seulgi Lee, Hyun-Sook Park, Seung Hun Jeong, Jin Han, Ji Young Mun, Kyung Soo Ko, Joon Sig Choi
Mitochondria dysfunction plays a role in many human diseases. Therapeutic techniques for these disorders require novel delivery systems that can specifically target and penetrate mitochondria. In this study, we report a novel nanosome composed of dequalinium-DOTAP-DOPE (1,2 dioleoyl-3-trimethylammonium-propane-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) (DQA80s) as a potential mitochondria-targeting delivery vector. The functional DQAsome, DQA80s, showed enhanced transfection efficiency compared to a vector DQAsomes in HeLa cells and dermal fibroblasts...
June 29, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28655658/multifunctional-peptide-lipid-nanocomplexes-for-efficient-targeted-delivery-of-dna-and-sirna-into-breast-cancer-cells
#14
Yu Wan, Wei Dai, Reshma J Nevagi, Istvan Toth, Peter M Moyle
The development of carriers for the delivery of oligonucleotide therapeutics is essential for the successful translation of gene therapies to the clinic. In the present study, a delivery system, which combines the fusogenic lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) with a well-defined synthetic multifunctional peptide, was produced and optimized for gene delivery, with the aim to develop an efficient gene delivery platform for breast cancer cells. For this purpose, a breast cancer-specific cell targeting peptide (CTP) was incorporated into our leading peptide-based gene delivery system (to generate DEN-K(GALA)-TAT-K(STR)-CTP) to improve its cell-specific internalization, and investigated in combination with a formulation approach (DOPE/1,2-dioleoyl-3-trimethylammonium-propane (DOTAP))...
September 1, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28652397/b-cells-produce-type-1-ifns-in-response-to-the-tlr9-agonist-cpg-a-conjugated-to-cationic-lipids
#15
Munir Akkaya, Billur Akkaya, Pietro Miozzo, Mukul Rawat, Mirna Pena, Patrick W Sheehan, Ann S Kim, Olena Kamenyeva, Juraj Kabat, Silvia Bolland, Akanksha Chaturvedi, Susan K Pierce
B cells express the innate receptor, TLR9, which signals in response to unmethylated CpG sequences in microbial DNA. Of the two major classes of CpG-containing oligonucleotides, CpG-A appears restricted to inducing type 1 IFN in innate immune cells and CpG-B to activating B cells to proliferate and produce Abs and inflammatory cytokines. Although CpGs are candidates for adjuvants to boost innate and adaptive immunity, our understanding of the effect of CpG-A and CpG-B on B cell responses is incomplete. In this study we show that both CpG-B and CpG-A activated B cells in vitro to proliferate, secrete Abs and IL-6, and that neither CpG-B nor CpG-A alone induced type 1 IFN production...
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28639178/effective-skin-cancer-treatment-by-topical-co-delivery-of-curcumin-and-stat3-sirna-using-cationic-liposomes
#16
Anup Jose, Suman Labala, Kunal Manoj Ninave, Sudeep Kumar Gade, Venkata Vamsi Krishna Venuganti
The aim of the present study was to evaluate the effectiveness of iontophoretic co-delivery of curcumin and anti-STAT3 siRNA using cationic liposomes against skin cancer. Curcumin was encapsulated in DOTAP-based cationic liposomes and then complexed with STAT3 siRNA. This nanocomplex was characterized for the average particle size, zeta-potential, and encapsulation efficiency. The cell viability studies in B16F10 mouse melanoma cells have shown that the co-delivery of curcumin and STAT3 siRNA significantly (p < 0...
June 21, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28636657/novel-sirna-formulation-to-effectively-knockdown-mutant-p53-in-osteosarcoma
#17
Anup K Kundu, Swathi V Iyer, Sruti Chandra, Amit S Adhikari, Tomoo Iwakuma, Tarun K Mandal
OBJECTIVES: The tumor suppressor p53 plays a crucial role in the development of osteosarcoma. The primary objective of this study is to develop and optimize lipid based nanoparticle formulations that can carry siRNA and effectively silence mutant p53 in 318-1, a murine osteosarcoma cell line. METHODS: The nanoparticles were composed of a mixture of two lipids (cholesterol and DOTAP) and either PLGA or PLGA-PEG and prepared by using an EmulsiFlex-B3 high pressure homogenizer...
2017: PloS One
https://www.readbyqxmd.com/read/28578092/construction-of-human-masp-2-ccp1-2sp-ccp2sp-sp-plasmid-dna-nanolipoplexes-and-the-effects-on-tuberculosis-in-bcg-infected-mice
#18
Qi Gao, Xinfang Dong, Yanping Luo, Guochao Zhang, Jinyu Shan, Qian Wang, Qi He, Lifeng Zhang, Jingqiu Wang, Bingdong Zhu, Xingming Ma
The lectin pathway, one of the complement cascade systems, provides the primary line of defense against invading pathogens. The serine protease of MASP-2 plays an essential role in complement activation of the lectin pathway. The C-terminal segment of MASP-2 is comprised of the CCP1-CCP2-SP domains, and is the crucial catalytic segment. However, what is the effect of CCP1-CCP2-SP domains in controlling chronic infection is unknown. In order to evaluate the potential impact of CCP1-CCP2-SP domains on tuberculosis, we constructed the human MASP-2 CCP1/2SP, CCP2SP and SP recombinant plasmids, and delivered these plasmids by DNA-DOTAP:cholesterol cationic nanolipoplexes to BCG-infected mice...
May 31, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28550752/intracellular-delivery-of-oligonucleotides-in-helicobacter-pylori-by-fusogenic-liposomes-in-the-presence-of-gastric-mucus
#19
Rita S Santos, George R Dakwar, Elisa Zagato, Toon Brans, Céu Figueiredo, Koen Raemdonck, Nuno F Azevedo, Stefaan C De Smedt, Kevin Braeckmans
The rising antimicrobial resistance contributes to 25000 annual deaths in Europe. This threat to the public health can only be tackled if novel antimicrobials are developed, combined with a more precise use of the currently available antibiotics through the implementation of fast, specific, diagnostic methods. Nucleic acid mimics (NAMs) that are able to hybridize intracellular bacterial RNA have the potential to become such a new class of antimicrobials and additionally could serve as specific detection probes...
September 2017: Biomaterials
https://www.readbyqxmd.com/read/28530287/microfluidic-self-assembly-of-folate-targeted-monomolecular-sirna-lipid-nanoparticles
#20
R Krzysztoń, B Salem, D J Lee, G Schwake, E Wagner, J O Rädler
Non-viral delivery of nucleic acids for therapies based on RNA interference requires a rational design and optimal self-assembly strategies. Nucleic acid particles need to be small, stable and functional in terms of selective cell uptake and controlled release of encapsulated nucleic acids. Here we report on small (∼38 nm) monomolecular nucleic acid/lipid particles (mNALPs) that contain single molecules of short double-stranded oligonucleotides covered by a tight, highly curved lipid bilayer. The particles consist of DOPE, DOTAP, DOPC and DSPE-PEG(2000) and are assembled with 21 bp double-stranded DNA or small interfering RNA by solvent exchange on a hydrodynamic-focusing microfluidic chip...
June 8, 2017: Nanoscale
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