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Blood brain barrier and liposomes

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 analyze 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 (12-14 nm in diameter) with high surface charge density, and bind to small (SUVs, about 24 nm in diameter) and large (LUV, about 100 nm in diameter) liposomes at variable lipid to peptide ratios...
October 1, 2016: European Journal of Pharmaceutics and Biopharmaceutics
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 which 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...
October 4, 2016: Molecular Pharmaceutics
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...
September 16, 2016: European Journal of Pharmaceutical Sciences
Alireza Partoazar, Sanaz Nasoohi, Sayed Mehdi Rezayat, Kambiz Gilani, Shahram Ejtemaei Mehr, Amir Amani, Nastaran Rahimi, Ahmad Reza Dehpour
Cyclosporin A (CsA) is known as a neuroprotective agent against cerebral ischemia/reperfusion (I/R) in animal models. However, the significant therapeutic effects of CsA have been observed in high systemic doses or manipulating the blood brain barrier (BBB), resulting in systemic side effects and toxicity. Since the liposome nanocarries have been developed for efficient delivery of peptide and proteins, liposomal CsA (Lipo-CsA) could improve cerebral (I/R) injuries. In this study, the liposomal CsA formulation (CsA at dose of 2...
September 12, 2016: Fundamental & Clinical Pharmacology
Hongmei Xia, Zhiqing Cheng, Yongfeng Cheng, Yinxiang Xu
Tetramethylpyrazine (TMP) is a natural product extracted from Rhizoma Chuanxiong. Liposomes are an excellent delivery method that is suitable for the penetration of the blood-brain barrier (BBB). TMP-loaded liposomes are suitable for the treatment of cerebral ischemic diseases. We measured the morphology, particle size, zeta-potential, entrapment efficiency, and content of TMP-loaded liposome. The electrochemical method was adopted to determine entrapment efficiency for the first time. In addition, their diffusion through BBB models, which were built not only by in vitro cell culture but also by the ex vivo mouse subcutaneous-mucous-membrane (mSMM) method, was explored...
December 1, 2016: Materials Science & Engineering. C, Materials for Biological Applications
S Cunha, M H Amaral, J M Sousa Lobo, A C Silva
Alzheimer's and Parkinson's diseases are prevalent neurodegenerative disorders worldwide, which are essentially related to aging. Within the remarkable era of nanomedicine, nowadays several delivery systems have been suggested to improve the treatment of these disorders, namely, liposomes, micelles, nanoparticles (polymeric, lipid, metallic and inorganic), exosomes, dendrimers and fullerenes. The advantage that has been claimed to these delivery systems is that they facilitate the passage of drugs through the blood brain barrier (BBB), enabling targeting before body degradation, and increasing therapeutic efficacy, comparing to conventional pharmaceutical dosage forms...
August 24, 2016: Current Medicinal Chemistry
Robin Tremmel, Philipp Uhl, Frieder Helm, Dominik Wupperfeld, Max Sauter, Walter Mier, Wolfgang Stremmel, Götz Hofhaus, Gert Fricker
The existence of the blood-brain barrier (BBB) complicates the treatment of many central nervous system (CNS) disorders, including the copper storage disease, Wilson's disease. Its CNS symptoms represent a serious problem, since therapeutics for Wilson's disease do not cross the BBB. One strategy to overcome this obstacle is the transfer of drugs across the BBB with colloidal carrier systems like liposomes. The aim of the present study was to encapsulate triethylenetetramine (TETA), a copper chelating agent, into surface modified liposomes and to investigate their permeation across the BBB...
October 15, 2016: International Journal of Pharmaceutics
Heather R Bender, Sarah Kane, Mark D Zabel
Prion diseases result from the misfolding of the normal, cellular prion protein (PrP(C)) to an abnormal protease resistant isomer called PrP(Res). The emergence of prion diseases in wildlife populations and their increasing threat to human health has led to increased efforts to find a treatment for these diseases. Recent studies have found numerous anti-prion compounds that can either inhibit the infectious PrP(Res) isomer or down regulate the normal cellular prion protein. However, most of these compounds do not cross the blood brain barrier to effectively inhibit PrP(Res) formation in brain tissue, do not specifically target neuronal PrP(C), and are often too toxic to use in animal or human subjects...
2016: Journal of Visualized Experiments: JoVE
M Sánchez-Purrà, V Ramos, V A Petrenko, V P Torchilin, S Borrós
In order to treat metastasis in the brain, drug delivery systems must overcome multiple physical barriers between the point of administration and the target, such as the Blood-brain barrier, that hinder their free access across them. Multiple targeting approaches arise as a promising alternative to this barrier and target certain tissues inside the brain at a time. Herein, two surface modification methods are presented to obtain dual-targeted vesicle-like carriers functionalized with an MCF-7-specific phage protein and a BBB-specific peptide, providing the system the ability to cross a BBB model, target breast cancer cells and deliver its payload...
September 25, 2016: International Journal of Pharmaceutics
Ichio Aoki
The advent of functional contrast agents and nanoparticle drug delivery systems (nano-DDS) is opening new pathways to understanding pathophysiology using magnetic resonance imaging (MRI). Nitroxyl radical compounds are promising functional contrast agents for redox evaluation. We have developed a novel nitroxyl radical theranostic compound for noninvasive real-time imaging of blood-brain barrier-permeable antitumor drugs. Divalent manganese ions (Mn(2+)) can also be used as an intracellular functional MRI contrast agent...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Huanling Liu, Anna Jablonska, Yuguo Li, Suyi Cao, Dexiang Liu, Hanwei Chen, Peter Cm Van Zijl, Jeff W M Bulte, Miroslaw Janowski, Piotr Walczak, Guanshu Liu
ABSTRACT Citicoline (CDPC) is a natural supplement with well-documented neuroprotective effects in the treatment of neurodegenerative diseases. In the present study, we sought to exploit citicoline as a theranostic agent with its inherent chemical exchange saturation transfer (CEST) MRI signal, which can be directly used as an MRI guidance in the citicoline drug delivery. Our in vitro CEST MRI results showed citicoline has two inherent CEST signals at +1 and +2 ppm, attributed to exchangeable hydroxyl and amine protons, respectively...
2016: Theranostics
Mireia Campos-Martorell, Mary Cano-Sarabia, Alba Simats, Mar Hernández-Guillamon, Anna Rosell, Daniel Maspoch, Joan Montaner
BACKGROUND AND AIMS: Although the beneficial effects of statins on stroke have been widely demonstrated both in experimental studies and in clinical trials, the aim of this study is to prepare and characterize a new liposomal delivery system that encapsulates simvastatin to improve its delivery into the brain. MATERIALS AND METHODS: In order to select the optimal liposome lipid composition with the highest capacity to reach the brain, male Wistar rats were submitted to sham or transitory middle cerebral arterial occlusion (MCAOt) surgery and treated (intravenous [IV]) with fluorescent-labeled liposomes with different net surface charges...
2016: International Journal of Nanomedicine
Darya Hadavi, André A Poot
Alzheimer's disease (AD) as a progressive and fatal neurodegenerative disease represents a huge unmet need for treatment. The low efficacy of current treatment methods is not only due to low drug potency but also due to the presence of various obstacles in the delivery routes. One of the main barriers is the blood-brain barrier. The increasing prevalence of AD and the low efficacy of current therapies have increased the amount of research on unraveling of disease pathways and development of treatment strategies...
2016: Frontiers in Bioengineering and Biotechnology
Lin Wei, Xi-Ying Guo, Ting Yang, Min-Zhi Yu, Da-Wei Chen, Jian-Cheng Wang
Treatment of brain tumor remains a great challenge worldwide. Development of a stable, safe, and effective siRNA delivery system which is able to cross the impermeable blood-brain barrier (BBB) and target glioma cells is necessary. This study aims to investigate the therapeutic effects of intravenous administration of T7 peptide modified core-shell nanoparticles (named T7-LPC/siRNA NPs) on brain tumors. Layer-by-layer assembling of protamine/chondroitin sulfate/siRNA/cationic liposomes followed by T7 peptide modification has been carried out in order to obtain a targeted siRNA delivery system...
August 20, 2016: International Journal of Pharmaceutics
Young-Sook Kang, Hyun-Joo Jung, Ji-Suk Oh, Dae-Yong Song
AIM: To treat neurodegenerative disorders such as Parkinson's disease (PD), drugs must be able to cross the blood-brain barrier (BBB). Patients with PD are deficient in dopamine (DA), a neurotransmitter that cannot pass through the BBB. Liposomes modified by adding polyethylene glycol (PEGylated liposomes (PLs)) can be conjugated with antibody to form DA-PEGylated immunoliposomes (DA-PILs), and we tested their use as carriers of DA for treating PD. METHODS: PEGylated liposomes (PLs) were prepared by evaporation method, and [(3) H]dopamine was encapsulated within the dried lipid film using a freeze/thaw cycle to form DA-PL...
October 2016: CNS Neuroscience & Therapeutics
Yoko Endo-Takahashi, Kotomi Ooaku, Kazuma Ishida, Ryo Suzuki, Kazuo Maruyama, Yoichi Negishi
In the development of therapeutic approaches for central nervous system diseases, a significant obstacle is efficient drug delivery across the blood-brain barrier owing to its low permeability. Various nanocarriers have been developed for brain-targeted drug delivery by modification with specific ligands. We have previously developed polyethylene glycol-modified liposomes (Bubble liposomes [BLs]) that entrap ultrasound (US) contrast gas and can serve as both plasmid DNA or small interfering RNA carriers and US contrast agents...
2016: Biological & Pharmaceutical Bulletin
Chung-Yin Lin, Han-Yi Hsieh, Chiung-Mei Chen, Shang-Rung Wu, Chih-Hung Tsai, Chiung-Yin Huang, Mu-Yi Hua, Kuo-Chen Wei, Chih-Kuang Yeh, Hao-Li Liu
Focused ultrasound (FUS)-induced with microbubbles (MBs) is a promising technique for noninvasive opening of the blood-brain barrier (BBB) to allow targeted delivery of therapeutic substances into the brain and thus the noninvasive delivery of gene vectors for CNS treatment. We have previously demonstrated that a separated gene-carrying liposome and MBs administration plus FUS exposure can deliver genes into the brain, with the successful expression of the reporter gene and glial cell line-derived neurotrophic factor (GDNF) gene...
August 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Liang Zhang, Amyn A Habib, Dawen Zhao
Phosphatidylserine (PS), which is normally intracellular, becomes exposed on the outer surface of viable endothelial cells (ECs) of tumor vasculature. Utilizing a PS-targeting antibody, we have recently established a PS-targeted liposomal (PS-L) nanoplatform that has demonstrated to be highly tumor-selective. Because of the vascular lumen-exposed PS that is immediately accessible without a need to penetrate the intact blood brain barrier (BBB), we hypothesize that the systemically administered PS-L binds specifically to tumor vascular ECs, becomes subsequently internalized into the cells and then enables its cargos to be efficiently delivered to glioma parenchyma...
May 25, 2016: Oncotarget
Ying Xing, Chun-Yan Wen, Song-Tao Li, Zong-Xin Xia
Brain-derived neurotrophic factor (BDNF) plays an important role in the repair of central nervous system injury, but cannot directly traverse the blood-brain barrier. Liposomes are a new type of non-viral vector, able to carry macromolecules across the blood-brain barrier and into the brain. Here, we investigate whether BDNF could be transported across the blood-brain barrier by tail-vein injection of liposomes conjugated to transferrin (Tf) and polyethylene glycol (PEG), and carrying BDNF modified with cytomegalovirus promoter (pCMV) or glial fibrillary acidic protein promoter (pGFAP) (Tf-pCMV-BDNF-PEG and Tf-pGFAP-BDNF-PEG, respectively)...
April 2016: Neural Regeneration Research
Yue Zhao, Yan Jiang, Wei Lv, Zhongyuan Wang, Lingyan Lv, Baoyan Wang, Xin Liu, Yang Liu, Quanyin Hu, Wujin Sun, Qunwei Xu, Hongliang Xin, Zhen Gu
Focal cerebral ischemia, known as stroke, causes serious long-term disabilities globally. Effective therapy for cerebral ischemia demands a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the ischemia area in brain. Here, we designed a novel neuroprotectant (ZL006) loaded dual targeted nanocarrier based on liposome (T7&SHp-P-LPs/ZL006) conjugated with T7 peptide (T7) and stroke homing peptide (SHp) for penetrating BBB and targeting ischemia area, respectively. Compared with non-targeting liposomes, T7&SHp-P-LPs/ZL006 could transport across BCEC cells and significantly enhance cellular uptake and reduce cells apoptosis of excitatory amino acid stimulated PC-12 cells...
July 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
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