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Blood brain barrier and liposomes

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https://www.readbyqxmd.com/read/28193538/multifunctional-luv-liposomes-decorated-for-bbb-and-amyloid-targeting-a-in-vitro-proof-of-concept
#1
Konstantina Papadia, Eleni Markoutsa, Spyridon Mourtas, Anastassios Giannou, Barabara La Ferla, Fransesco Nicotra, Mario Salmona, Pavlos Klepetsanis, Georgios T Stathopoulos, Sophia G Antimisiaris
Multifunctional LUV liposomes (mf-LIPs) were developed, having a curcumin-lipid ligand (TREG) with affinity towards amyloid species, together with ligands to target the transferrin and the LDL receptors of the blood-brain-barrier (BBB), on their surface. mf-LIPs were evaluated for their brain targeting, on hCMEC/D3 monolayers, and for their ability to inhibit Aβ-peptide aggregation. The transport of mf-LIP across hCMEC/D3 monolayers was similar to that of BBB-LIPs, indicating that the presence of TREG on their surface does not reduce their brain targeting potential...
February 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28101766/crossing-the-blood-brain-barrier-recent-advances-in-drug-delivery-to-the-brain
#2
Mayur M Patel, Bhoomika M Patel
CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting...
January 18, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28093036/combining-nanoscale-magnetic-nimodipine-liposomes-with-magnetic-resonance-image-for-parkinson-s-disease-targeting-therapy
#3
Bingshuo Ji, Meili Wang, Dawei Gao, Shanshan Xing, Lei Li, Lanxiang Liu, Min Zhao, Ximing Qi, Kun Dai
AIM: To enhance drug targeting and blood-brain barrier penetration for Parkinson's disease (PD), a novel nanoscale magnetic nimodipine (NMD) delivery system was designed and prepared. MATERIALS & METHODS: The PD rats were established and treated with free NMD or Fe3O4-modified NMD liposomes (Fe3O4-NMD-lips). Then, factional anisotropy values were measured by MRI to evaluate therapy efficacy. RESULTS: Fe3O4-NMD-lips showed the best neuroprotective effect, and the NMD concentration of lesions was 2...
January 17, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28088075/development-of-a-hypoxia-triggered-and-hypoxic-radiosensitized-liposome-as-a-doxorubicin-carrier-to-promote-synergetic-chemo-radio-therapy-for-glioma
#4
Hongmei Liu, Yandong Xie, Yafei Zhang, Yifan Cai, Baiyang Li, Honglin Mao, Yingguo Liu, Jun Lu, Longzhen Zhang, Rutong Yu
The treatment of malignant primary brain tumors is challenging. Concomitant radiochemotherapy has become the standard clinical treatment for malignant glioma, but there are two critical challenges to overcome in order to increase efficacy. First, glioma is known to have increased resistant to radiation due to its intra-tumoral hypoxia. In addition, the blood-brain barrier (BBB) restricts the distribution of the chemotherapeutic agent to the brain. Therefore, we developed a hypoxic radiosensitizer-prodrug liposome (MLP), in order to deliver DOX to the tumor and to overcome the above challenges, achieving a synergistic chemo-/radiotherapy treatment of malignant glioma...
March 2017: Biomaterials
https://www.readbyqxmd.com/read/28069201/pulsed-wave-low-dose-ultrasound-hyperthermia-selectively-enhances-nanodrug-delivery-and-improves-antitumor-efficacy-for-brain-metastasis-of-breast-cancer
#5
Sheng-Kai Wu, Chi-Feng Chiang, Yu-Hone Hsu, Houng-Chi Liou, Wen-Mei Fu, Win-Li Lin
The clinical application of chemotherapeutics for brain tumors remains a challenge due to limitation of blood-brain barrier/blood-tumor barrier (BBB/BTB). In this study, we investigated the effects of low-dose focused ultrasound hyperthermia (UH) on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer cells (4T1-luc2) expressing firefly luciferase were implanted into mouse striatum as a brain tumor model. The mice were intravenously injected with PLD with/without transcranial pulsed-wave/continuous-wave UH (pUH/cUH) treatment on day-6 after tumor implantation...
May 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28025942/nano-medicine-improving-the-bioavailability-of-small-molecules-for-the-prevention-of-neurodegenerative-diseases
#6
Piera Di Martino, Roberta Censi, Maria Rosa Gigliobianco, Luana Zerrillo, Federico Magnoni, Dimitrios Agas, Wilma Quaglia, Giulio Lupidi
Neurodegenerative diseases, including Parkinson's and Alzheimer's, are a heterogeneous group of brain disorders characterized by the progressive degeneration of the structure and function of the central or peripheral nervous system. It is thought that the number of people affected by these pathologies will increase in future decades, particularly in the more economically developed countries, where the populations are experiencing a demographic shift towards older ages. For many of these pathologies, and in particular for Alzheimer's disease, no effective treatments are available, and the consequent economic and social costs are very high...
December 27, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28008255/rescuing-cholinergic-neurons-from-apoptotic-degeneration-by-targeting-of-serotonin-modulator-and-apolipoprotein-e-conjugated-liposomes-to-the-hippocampus
#7
Yung-Chih Kuo, Yin-Jung Lee
β-Amyloid (Aβ)-targeting liposomes (LIP) with surface serotonin modulator (SM) and apolipoprotein E (ApoE) were utilized to facilitate the delivery of nerve growth factor (NGF) across the blood-brain barrier (BBB) for neuroprotection in the hippocampus. The therapeutic efficacy of SM- and ApoE-grafted LIP carrying NGF (NGF-SM-ApoE-LIP) was assessed by an in vitro Alzheimer's disease (AD) model of degenerated SK-N-MC cells and an in vivo AD model of Aβ-insulted Wistar rats. The experimental evidences revealed that the modified SM and ApoE on the surface of LIP increased the permeation of NGF across the BBB without serious damage to structural integrity of tight junction...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28003011/targeting-the-brain-with-nanomedicine
#8
Felix Rueda, Luis J Cruz
Herein, we review innovative nanomedicine-based approaches for treating, preventing and diagnosing neurodegenerative diseases. We focus on nanoscale systems such as polymeric nanoparticles (NPs), liposomes, micelles and other vehicles (e.g. dendrimers, nanogels, nanoemulsions and nanosuspensions) for targeted delivery of bioactive molecules to the brain. To ensure maximum selectivity for optimal therapeutic or diagnostic results, researchers must employ delivery systems that are non-toxic, biodegradable and biocompatible...
December 21, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28002997/targeting-the-brain-with-nanomedicine
#9
Felix Rueda, Luis J Cruz
Herein, we review innovative nanomedicine-based approaches for treating, preventing and diagnosing neurodegenerative diseases. We focus on nanoscale systems such as polymeric nanoparticles (NPs), liposomes, micelles and other vehicles (e.g. dendrimers, nanogels, nanoemulsions and nanosuspensions) for targeted delivery of bioactive molecules to the brain. To ensure maximum selectivity for optimal therapeutic or diagnostic results, researchers must employ delivery systems that are non-toxic, biodegradable and biocompatible...
December 21, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27986226/glutathione-conjugation-dose-dependently-increases-brain-specific-liposomal-drug-delivery-in-vitro-and-in-vivo
#10
David Maussang, Jaap Rip, Joan van Kregten, Angelique van den Heuvel, Susanne van der Pol, Burt van der Boom, Arie Reijerkerk, Linda Chen, Marco de Boer, Pieter Gaillard, Helga de Vries
The blood-brain barrier (BBB) represents a major obstacle for the delivery and development of drugs curing brain pathologies. However, this biological barrier presents numerous endogenous specialized transport systems that can be exploited by engineered nanoparticles to enable drug delivery to the brain. In particular, conjugation of glutathione (GSH) onto PEGylated liposomes (G-Technology(®)) showed to safely enhance delivery of encapsulated drugs to the brain. Yet, understanding of the mechanism of action remains limited and full mechanistic understanding will aid in the further optimization of the technology...
June 2016: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/27986225/liposome-technologies-and-drug-delivery-to-the-cns
#11
REVIEW
Jaap Rip
Brain and nervous system disorders represent a large unmet medical need. Central nervous system drug development is hampered by the restricted transport of drugs across the blood-brain barrier. Different strategies to deliver drugs to the brain have been developed. We discuss the current status of development of liposomal drug delivery to the brain. There is a growing interest in targeted delivery of liposomes to the brain and much progress has been made towards successful development of novel treatments for patients with devastating brain diseases...
June 2016: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/27916828/enhancing-anticancer-effect-of-gefitinib-across-the-blood-brain-barrier-model-using-liposomes-modified-with-one-%C3%AE-helical-cell-penetrating-peptide-or-glutathione-and-tween-80
#12
Kuan-Hung Lin, Shu-Ting Hong, Hsiang-Tsui Wang, Yu-Li Lo, Anya Maan-Yuh Lin, James Chih-Hsin Yang
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib, have been demonstrated to effectively treat the patients of extracranial non-small cell lung cancer (NSCLC). However, these patients often develop brain metastasis (BM) during their disease course. The major obstacle to treat BM is the limited penetration of anticancer drugs across the blood-brain barrier (BBB). In the present study, we utilized gefitinib-loaded liposomes with different modifications to improve gefitinib delivery across the in vitro BBB model of bEnd...
November 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27884636/an-in-vitro-and-in-vivo-study-of-peptide-functionalized-nanoparticles-for-brain-targeting-the-importance-of-selective-blood-brain-barrier-uptake
#13
Gerard H Bode, Gregory Coué, Christian Freese, Karin E Pickl, Maria Sanchez-Purrà, Berta Albaiges, Salvador Borrós, Ewoud C van Winden, Leto-Aikaterini Tziveleka, Zili Sideratou, Johan F Engbersen, Smriti Singh, Krystyna Albrecht, Jürgen Groll, Martin Möller, Andy J G Pötgens, Christoph Schmitz, Eleonore Fröhlich, Christian Grandfils, Frank M Sinner, C James Kirkpatrick, Harry W M Steinbusch, Hans-Georg Frank, Ronald E Unger, Pilar Martinez-Martinez
Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo...
November 21, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27799765/getting-into-the-brain-liposome-based-strategies-for-effective-drug-delivery-across-the-blood-brain-barrier
#14
REVIEW
Débora B Vieira, Lionel F Gamarra
This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood-brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer's, Parkinson's, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27797175/liposome-based-systemic-glioma-targeted-drug-delivery-enabled-by-all-d-peptides
#15
Man Ying, Changyou Zhan, Songli Wang, Bingxin Yao, Xuefeng Hu, Xianfei Song, Mingfei Zhang, Xiaoli Wei, Yan Xiong, Weiyue Lu
As the most aggressive brain tumor, chemotherapy of malignant glioma remains to be extremely challenging in clinic. The blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) are physiological and pathological barriers preventing therapeutic drugs from reaching the glioma region. In addition, vasculogenic mimicry (VM) formed by invasive glioma cells instead of endothelial cells and angiogenesis are very common in glioma, leading to the poor prognosis and recurrence of glioma. An ideal drug delivery system for glioma chemotherapy needs to traverse the BBB and BBTB and then target VM, angiogenesis, and glioma cells...
November 9, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27784243/brain-drug-delivery-systems-for-the-stroke-intervention-and-recovery
#16
Tiantian Luo, Ju Wang, Shilei Hao, Tingwang Guo, Peng Ren, Zhongjun Cheng, Feiyan Gao, Yuhua Gong, Bochu Wang
BACKGROUND: Stroke remains the second commonest cause of death and leading cause of adult disability worldwide. Ischemic events account for nearly 85% of all strokes, and hemorrhages account for nearly 15%. Stroke intervention and recovery have been identified as the important factors in the functional outcome of patients with completed stroke. However, the only FDA approved treatment for ischemic strokes is tissue plasminogen activator, and no effective targeted therapy for hemorrhagic stroke exists yet...
October 25, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27769888/retro-inverso-peptide-inhibitor-nanoparticles-as-potent-inhibitors-of-aggregation-of-the-alzheimer-s-a%C3%AE-peptide
#17
Maria Gregori, Mark Taylor, Elisa Salvati, Francesca Re, Simona Mancini, Claudia Balducci, Gianluigi Forloni, Vanessa Zambelli, Silvia Sesana, Maria Michael, Christos Michail, Claire Tinker-Mill, Oleg Kolosov, Michael Sherer, Stephen Harris, Nigel J Fullwood, Massimo Masserini, David Allsop
Aggregation of amyloid-β peptide (Aβ) is a key event in the pathogenesis of Alzheimer's disease (AD). We investigated the effects of nanoliposomes decorated with the retro-inverso peptide RI-OR2-TAT (Ac-rGffvlkGrrrrqrrkkrGy-NH2) on the aggregation and toxicity of Aβ. Remarkably low concentrations of these peptide inhibitor nanoparticles (PINPs) were required to inhibit the formation of Aβ oligomers and fibrils in vitro, with 50% inhibition occurring at a molar ratio of ~1:2000 of liposome-bound RI-OR2-TAT to Aβ...
October 19, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27702684/lipopeptide-based-micellar-and-liposomal-carriers-influence-of-surface-charge-and-particle-size-on-cellular-uptake-into-blood-brain-barrier-cells
#18
Karl Sydow, Heike Nikolenko, Dorothea Lorenz, Rainer H Müller, Margitta Dathe
Lipopeptide-based micelles and liposomes were found to differ in cell recognition and uptake mode into blood brain barrier (BBB) endothelial cells. Here we analyse the role of size and surface charge of micelles and liposomes composed of different lipopeptide sequences with respect to uptake into human brain capillary (HBMEC) and aortic (HAoEC) endothelial cells. Comparable to the dipalmitoylated apolipoprotein E-derived P2A2, lipopeptides of cationic poly-arginine (P2Rn), poly-lysine (P2Kn) and an anionic glutamic-acid sequence (P2En) self assemble into micelles (12-14nm in diameter) with high surface charge density, and bind to small (SUVs, about 24nm in diameter) and large (LUV, about 100nm in diameter) liposomes at variable lipid to peptide ratios...
December 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27700119/biomimetic-apoe-reconstituted-high-density-lipoprotein-nanocarrier-for-blood-brain-barrier-penetration-and-amyloid-beta-targeting-drug-delivery
#19
Qingxiang Song, Huahua Song, Jianrong Xu, Jialin Huang, Meng Hu, Xiao Gu, Juan Chen, Gang Zheng, Hongzhuan Chen, Xiaoling Gao
Amyloid beta (Aβ) and its aggregation forms in the brain have been suggested as key targets for the therapy of Alzheimer's disease (AD). Therefore, the development of nanocarriers that possess both blood-brain barrier permeability and Aβ-targeting ability is of great importance for the intervention of AD. Here we constructed a biomimetic nanocarrier named apolipoprotein E (ApoE)-reconstituted high density lipoprotein nanocarrier (ANC) from recombinant ApoE and synthetic lipids to achieve the above goals. α-Mangostin (α-M), a polyphenolic agent that can inhibit the formation of Aβ oligomers and fibrils and accelerate Aβ cellular degradation, was used as the model drug...
November 7, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27644895/targeting-vincristine-plus-tetrandrine-liposomes-modified-with-dspe-peg2000-transferrin-in-treatment-of-brain-glioma
#20
Xiao-Li Song, Shuang Liu, Ying Jiang, Li-Yan Gu, Yao Xiao, Xin Wang, Lan Cheng, Xue-Tao Li
Glioma is the most frequent primary tumor, and the treatment efficiency is unsatisfactory for the obstacle of the blood brain barrier (BBB), the multidrug resistance (MDR) and the properties of cancer cell invasion and vasculogenic mimicry (VM) formation. In this study, a kind of TF modified vincristine plus tetrandrine liposomes was developed to overcome those limitations. In vitro results showed that TF modified vincristine plus tetrandrine liposomes with suitable physicochemical property could enhance the transport across the BBB, increase the cellular uptake, inhibit the MDR, and block the cancer cell invasion and VM channels...
January 1, 2017: European Journal of Pharmaceutical Sciences
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