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https://www.readbyqxmd.com/read/29165590/miltefosine-resistant-leishmania-infantum-strains-with-an-impaired-mt-ros3-transporter-complex-retain-amphotericin-b-susceptibility
#1
Annelies Mondelaers, Sarah Hendrickx, Lieselotte Van Bockstal, Louis Maes, Guy Caljon
Objectives: Increasing numbers of miltefosine treatment failures in visceral leishmaniasis therapy and reports of miltefosine resistance in the Indian subcontinent resulted in the recommendation to use liposomal amphotericin B as first-line therapy. Cross-resistance between miltefosine and amphotericin B has recently been documented, suggesting a role of mutations in the miltefosine transporter, a complex encoded by the MT and ROS3 genes. This study aimed to further explore the putative role of MT/ROS3 defects in the molecular basis of amphotericin B cross-resistance...
November 18, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29164606/safety-and-efficacy-of-pomalidomide-dexamethasone-and-pegylated-liposomal-doxorubicin-for-patients-with-relapsed-or-refractory-multiple-myeloma
#2
Alexa Cohen, Tanya M Spektor, Laura Stampleman, Alberto Bessudo, Peter J Rosen, Leonard M Klein, Thomas Woliver, Marshall Flam, Shahrooz Eshaghian, Youram Nassir, Tina Maluso, Regina A Swift, Robert Vescio, James R Berenson
Immunomodulatory drugs including thalidomide, lenalidomide (LEN) and pomalidomide (POM), are effective for treating multiple myeloma (MM). POM has shown enhanced efficacy with dexamethasone (DEX). Pegylated liposomal doxorubicin (PLD) with bortezomib is US Food and Drug Administration-approved for treating MM. PLD with LEN or thalidomide has shown efficacy for MM patients. LEN with DEX, PLD and bortezomib achieves high response rates. We evaluated the combination of POM with DEX 40 mg and PLD 5 mg/m(2) with the latter two drugs administered on days 1, 4, 8 and 11 on a 28-day cycle for the treatment of relapsed/refractory MM patients...
November 21, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29164051/anti-inflammatory-microglia-macrophages-as-a-potential-therapeutic-target-in-brain-metastasis
#3
Kleopatra E Andreou, Manuel Sarmiento Soto, Danny Allen, Vasiliki Economopoulos, Axel de Bernardi, James R Larkin, Nicola R Sibson
Brain metastasis is a common complication of cancer patients and is associated with poor survival. Histological data from patients with brain metastases suggest that microglia are the major immune population activated around the metastatic foci. Microglia and macrophages have the ability to polarize to different phenotypes and to exert both tumorigenic and cytotoxic effects. However, the role of microglia/macrophages during the early stages of metastatic growth in the brain has not yet been determined. The aim of this study was to profile microglial/macrophage activation in a mouse model of breast cancer brain metastasis during the early stages of tumor growth, and to assess the role of the anti-inflammatory microglial/macrophage population, specifically, during this phase...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29163750/long-acting-liposomal-bupivacaine-for-percutaneous-sympathetic-stellate-ganglion-blockade-a-technical-note
#4
Adnan I Qureshi, Muhammad A Waqas, Vikram Jadhav, Muhammad A Saleem, Jeff Campbell, Shawn S Wallery
Introduction: We describe the use of long acting liposomal bupivacaine for percutaneous stellate ganglion blockade to treat severe headaches following internal carotid artery dissection. Methods: A 43-year old woman developed right-sided refractory headache after right internal carotid artery dissection. Patient underwent percutaneous stellate ganglion block using bupivacaine hydrochloride (0.25%-20 ml) in the past with short acting relief. Liposomal bupivacaine (EXPAREL) 13...
October 2017: Journal of Vascular and Interventional Neurology
https://www.readbyqxmd.com/read/29163174/sustained-complete-response-to-metronomic-chemotherapy-in-a-child-with-refractory-atypical-teratoid-rhabdoid-tumor-a-case-report
#5
Mahe Berland, Laetitia Padovani, Angélique Rome, Grégoire Pech-Gourg, Dominique Figarella-Branger, Nicolas André
Atypical teratoid rhabdoid tumor (ATRT) is a rare and highly aggressive embryonal tumor of the central nervous system with a dismal prognosis and no definitive guidelines for treatment, especially at relapse or in case of refractory disease. Metronomic chemotherapy (MC) has emerged as a new treatment option in solid malignancies, with lower toxicity and is frequently combined with drug repositioning. We report a case of ATRT in an 8-year-old boy who progressed during multimodal therapy including surgical resection, chemotherapy and radiotherapy...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29163138/perspective-insights-into-disease-progression-diagnostics-and-therapeutic-approaches-in-alzheimer-s-disease-a-judicious-update
#6
REVIEW
Arif Tasleem Jan, Mudsser Azam, Safikur Rahman, Angham M S Almigeiti, Duk Hwan Choi, Eun Ju Lee, Qazi Mohd Rizwanul Haq, Inho Choi
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive accumulation of β-amyloid fibrils and abnormal tau proteins in and outside of neurons. Representing a common form of dementia, aggravation of AD with age increases the morbidity rate among the elderly. Although, mutations in the ApoE4 act as potent risk factors for sporadic AD, familial AD arises through malfunctioning of APP, PSEN-1, and-2 genes. AD progresses through accumulation of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) in brain, which interfere with neuronal communication...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29162829/single-molecule-visualization-of-conformational-changes-and-substrate-transport-in-the-vitamin-b12-abc-importer-btucd-f
#7
Joris M H Goudsmits, Dirk Jan Slotboom, Antoine M van Oijen
ATP-binding cassette (ABC) transporters form the largest class of active membrane transport proteins. Binding and hydrolysis of ATP by their highly conserved nucleotide-binding domains drive conformational changes of the complex that mediate transport of substrate across the membrane. The vitamin B12 importer BtuCD-F in Escherichia coli is an extensively studied model system. The periplasmic soluble binding protein BtuF binds the ligand; the transmembrane and ATPase domains BtuCD mediate translocation. Here we report the direct observation at the single-molecule level of ATP, vitamin B12 and BtuF-induced events in the transporter complex embedded in liposomes...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29162508/targeted-delivery-of-nucleic-acids-into-xenograft-tumors-mediated-by-novel-folate-equipped-liposomes
#8
Tatyana O Kabilova, Elena V Shmendel, Daniil V Gladkikh, Elena L Chernolovskaya, Oleg V Markov, Nina G Morozova, Mikhail A Maslov, Marina A Zenkova
Folate receptors (FR) are cellular markers highly expressed in various cancer cells. Here, we report on the synthesis of a novel folate-containing lipoconjugate (FC) built of 1,2-di-O-ditetradecyl-rac-glycerol and folic acid connected via a PEG spacer, and the evaluation of the FC as a targeting component of liposomal formulations for nucleic acid (NA) delivery into FR expressing tumor cells. FR-targeting liposomes, based on polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosan tetrahydrochloride (2X3), lipid helper dioleoylphosphatidylethanolamine (DOPE) and novel FC, formed small compact particles in solution with diameters of 60 ± 22 nm, and were not toxic to cells...
November 18, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29162480/dual-targeting-immunoliposomes-using-angiopep-2-and-cd133-antibody-for-glioblastoma-stem-cells
#9
Jung Seok Kim, Dae Hwan Shin, Jin-Seok Kim
Glioblastoma stem cells (GSCs), which are identified as subpopulation of CD133(+)/ALDH1(+), are known to show resistance to the most of chemotherapy and radiation therapy, leading to the recurrence of tumor in glioblastoma multiforme (GBM) patients. Also, delivery of temozolomide (TMZ), a mainline treatment of GBM, to the GBM site is hampered by various barriers including the blood-brain barrier (BBB). A dual-targeting immunoliposome encapsulating TMZ (Dual-LP-TMZ) was developed by using angiopep-2 (An2) and anti-CD133 monoclonal antibody (CD133 mAb) for BBB transcytosis and specific delivery to GSCs, respectively...
November 18, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29162478/liposomes-assembled-from-dimeric-retinoic-acid-phospholipid-with-improved-pharmacokinetic-properties
#10
Lu Lu, Yawei Du, Muhammad Ismail, Longbing Ling, Chen Yao, Zhenglin Fu, Xinsong Li
All-trans-retinoic acid (ATRA) exhibits potent cytotoxicities against different cancer cells by binding to retinoic acid receptors (RARs), which is regarded as the first example of targeted therapy in acute promyelocytic leukemia (APL). However, its extensive clinical applications have been limited because of poor aqueous solubility, short half-life time and side effects. In this report, dimeric ATRA phosphorylcholine prodrug (Di-ATRA-PC) was designed and assembled into nanoliposomes to improve its pharmacokinetic properties...
November 18, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29162447/co-administration-of-liposomal-fasudil-and-tissue-plasminogen-activator-ameliorated-ischemic-brain-damage-in-occlusion-model-rats-prepared-by-photochemically-induced-thrombosis
#11
Tatsuya Fukuta, Yosuke Yanagida, Tomohiro Asai, Naoto Oku
Delivery of neuroprotectants with liposomes has been shown to be effective for the treatment of ischemic stroke. We have recently revealed that intravenous administration of liposomal fasudil (Fasudil-Lip), a Rho-kinase inhibitor, prior to thrombolysis with tissue plasminogen activator (t-PA) can extend the narrow therapeutic time window (TTW) of t-PA. In the present study, we examined the influence of t-PA treatment on liposomal accumulation into the ischemic region and cerebroprotective effect of combined treatment with Fasudil-Lip and t-PA performed at the same timing after the onset of ischemia in middle cerebral artery occlusion (MCAO) prepared by photochemically induced thrombosis...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29161719/palmitic-acid-curcumin-ester-facilitates-protection-of-neuroblastoma-against-oligomeric-a%C3%AE-40-insult
#12
Zhangyang Qi, Meihao Wu, Yun Fu, Tengfei Huang, Tingting Wang, Yanjie Sun, Zhibo Feng, Changzheng Li
BACKGROUND/AIMS: The generation of reactive oxygen species (ROS) caused by amyloid-β (Aβ) is considered to be one of mechanisms underlying the development of Alzheimer's disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aβ...
November 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29161215/recent-advances-in-nanomedicine-and-survivin-targeting-in-brain-cancers
#13
Jake Mazur, Kislay Roy, Jagat R Kanwar
Brain cancer is a highly lethal disease, especially devastating toward both the elderly and children. This cancer has no therapeutics available to combat it, predominately due to the blood-brain barrier (BBB) preventing treatments from maintaining therapeutic levels within the brain. Recently, nanoparticle technology has entered the forefront of cancer therapy due to its ability to deliver therapeutic effects while potentially passing physiological barriers. Key nanoparticles for brain cancer treatment include glutathione targeted PEGylated liposomes, gold nanoparticles, superparamagnetic iron oxide nanoparticles and nanoparticle-albumin bound drugs, with these being discussed throughout this review...
November 21, 2017: Nanomedicine
https://www.readbyqxmd.com/read/29161013/intelligent-peptide-gathering-mechanical-arm-tames-wild-trojan-horse-peptides-for-the-controlled-delivery-of-cancer-nanotherapeutics
#14
Nian-Qiu Shi, Yan Li, Yong Zhang, Nan Shen, Ling Qi, Shu-Ran Wang, Xian-Rong Qi
Cell-penetrating peptides (CPPs), also called "Trojan-Horse" peptides, have been used for facilitating intracellular delivery of numerous diverse cargoes and even nanocarriers. However, the lack of targeting specificity ("wildness" or nonselectivity) of CPP-nanocarriers remains an intractable challenge for many in vivo applications. In this work, we used an intelligent "peptide-gathering mechanical arm" (Int PMA) to curb CPPs' wildness and enhance the selectivity of R9-liposome-based cargo delivery for tumor targeting...
November 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29160717/reprogramming-tumor-associated-macrophages-to-reverse-egfr-t790m-resistance-by-dual-targeting-codelivery-of-gefitinib-vorinostat
#15
Huige Peng, Binfan Chen, Wei Huang, Yubo Tang, Yifan Jiang, Wenyuan Zhang, Yongzhuo Huang
Gefitinib is a first-line therapy in the EGFR-mutated nonsmall cell lung cancer (NSCLC). However, the development of drug resistance is almost unavoidable, thus leading to an unsustainable regimen. EGFR(T790M) mutation is the major cause responsible for the molecular-targeting therapy failure in NSCLC. Although the recently approved osimertinib is effective for the EGFR(T790M)-positive NSCLC, the osimertinib-resistant EGFR mutation is rapidly developed, too. In this study, we proposed a tumor-associated macrophage (TAM) reprogramming strategy for overcoming the EGFR(T790M)-associated drug resistance via a dual-targeting codelivery system of gefitinib/vorinostat that acted on both TAM with overexpression of mannose receptors and the HER-2 positive NSCLC cells...
November 21, 2017: Nano Letters
https://www.readbyqxmd.com/read/29160134/surfactant-protein-a-nanobody-conjugated-liposomes-loaded-with-methylprednisolone-increase-lung-targeting-specificity-and-therapeutic-effect-for-acute-lung-injury
#16
Nan Li, Dong Weng, Shan-Mei Wang, Yuan Zhang, Shan-Shan Chen, Zhao-Fang Yin, Jiali Zhai, Judy Scoble, Charlotte C Williams, Tao Chen, Hui Qiu, Qin Wu, Meng-Meng Zhao, Li-Qin Lu, Xavier Mulet, Hui-Ping Li
The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS-NSSLs-SPANb...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29158822/liposomal-64-cu-pet-imaging-of-anti-vegf-drug-effects-on-liposomal-delivery-to-colon-cancer-xenografts
#17
Stephanie J Blocker, Kirk A Douglas, Lisa Anne Polin, Helen Lee, Bart S Hendriks, Enxhi Lalo, Wei Chen, Anthony F Shields
Liposomes (LP) deliver drug to tumors due to enhanced permeability and retention (EPR). LP were labeled with (64)Cu for positron emission tomography (PET) to image tumor localization. Bevacizumab (bev), a VEGF targeted antibody, may modify LP delivery by altering tumor EPR and this change can also be imaged. Objective: Assess the utility of (64)Cu-labeled LP for PET in measuring altered LP delivery early after treatment with bev. Methods: HT-29 human colorectal adenocarcinoma tumors were grown subcutaneously in SCID mice...
2017: Theranostics
https://www.readbyqxmd.com/read/29158713/formulation-and-characterization-of-novel-soft-nanovesicles-for-enhanced-transdermal-delivery-of-eprosartan-mesylate
#18
Abdul Ahad, Abdulmohsen A Al-Saleh, Abdullah M Al-Mohizea, Fahad I Al-Jenoobi, Mohammad Raish, Alaa Eldeen B Yassin, Mohd Aftab Alam
The objective of the present work was to formulate, optimize and evaluate the potential of novel soft nanovesicles i.e. nano-transfersomes, containing eprosartan mesylate (EM) for transdermal delivery. Nano-transfersomes of EM were developed using Phospholipon 90G, Span 80 (SP) and sodium deoxycholate (SDC) and characterized for vesicle size, shape, entrapment efficiency, in vitro skin permeation study and confocal laser scanning microscopy. The optimized nano-transfersomes formulation showed vesicles size of 108...
November 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/29158706/comparative-study-of-free-and-liposome-entrapped-chloramphenicol-against-biofilms-of-potentially-pathogenic-bacteria-isolated-from-cooling-towers
#19
Marcus Vinícius Dias-Souza, Daniel Lucas Soares, Vera Lúcia Dos Santos
This study aimed to investigate for the first time the in vitro antibiofilm effectiveness of two chloramphenicol liposome formulations against biofilms of potentially pathogenic bacteria associated to corrosion isolated from the water of cooling towers from a Brazilian industry. Antibiofilm assays with liposomes were performed in 96-wells microtiter plates, and data was compared to free chloramphenicol treatment. Chloramphenicol-loaded liposomes were successfully produced using the dehydration-rehydration method, with vesicle diameters of 131 nm (100 nm membrane extrusion) and 182 nm (200 nm membrane extrusion) assessed by dynamic light scattering...
November 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/29158704/a-quality-by-design-approach-for-the-development-of-lyophilized-liposomes-with-simvastatin
#20
Alina Porfire, Dana Maria Muntean, Lucia Rus, Bianca Sylvester, Ioan Tomuţă
Lyophilization is used to ensure an increased shelf-life of liposomes, by preserving them in dry state, more stable than the aqueous dispersions. When stored as aqueous systems, the encapsulated drugs are released and the liposomes might aggregate or fuse. The aim of this study was to develop and optimize a lyophilized formulation of simvastatin (SIM) loaded into long circulating liposomes using the Quality by Design (QbD) approach. Pharmaceutical development by QbD aims to identify characteristics that are critical for the final product quality, and to establish how the critical process parameters can be varied to consistently produce a product with the desired characteristics...
November 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
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