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Liposome BBB

David J Lundy, Keng-Jung Lee, I-Chia Peng, Chia-Hsin Hsu, Jen-Hao Lin, Kun-Hung Chen, Yu-Wen Tien, Patrick C H Hsieh
The blood brain barrier (BBB) selectively controls the passage of endogenous and exogenous molecules between systemic circulation and the brain parenchyma. Nano-carrier based drugs such as liposomes and nanoparticles are an attractive prospect for cancer therapy since they can carry a drug payload and be modified to improve targeting and retention at the desired site. However, the BBB prevents most therapeutic drugs from entering the brain, including physically restricting the passage of liposomes and nanoparticles...
December 11, 2018: ACS Nano
Stephanie Andrade, Maria João Ramalho, Maria do Carmo Pereira, Joana A Loureiro
Resveratrol (RES) is a natural polyphenolic non-flavonoid compound present in grapes, mulberries, peanuts, rhubarb and in several other plants. Numerous health effects have been related with its intake, such as anti-carcinogenic, anti-inflammatory and brain protective effects. The neuroprotective effects of RES in neurological diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases, are related to the protection of neurons against oxidative damage and toxicity, and to the prevention of apoptotic neuronal death...
2018: Frontiers in Pharmacology
Grishma N Pawar, Neha N Parayath, Angela L Nocera, Benjamin S Bleier, Mansoor M Amiji
Delivering therapeutics across the blood-brain barrier (BBB) for treating central nervous system (CNS) diseases is one of the biggest challenges today as the BBB limits the uptake of molecules greater than 500 Da into the CNS. Here we describe a novel trans-nasal mucosal drug delivery as an alternative to the intranasal drug delivery to overcome its limitations and deliver high molecular weight (HMW) therapeutics efficiently to the brain. This approach is based on human endoscopic skull base surgical techniques in which a surgical defect is repaired by engrafting semipermeable nasal mucosa over a skull base defect...
2018: PloS One
You Jung Kang, Eric Gerard Cutler, Hansang Cho
The major neurological disorders found in a central nervous system (CNS), such as brain tumors, Alzheimer's diseases, Parkinson's diseases, and Huntington's disease, have led to devastating outcomes on the human public health. Of these disorders, early diagnostics remains poor, and no treatment has been successfully discovered; therefore, they become the most life-threatening medical burdens worldwide compared to other major diseases. The major obstacles for the drug discovery are the presence of a restrictive blood-brain barrier (BBB), limiting drug entry into brains and undesired neuroimmune activities caused by untargeted drugs, leading to irreversible neuronal damages...
November 30, 2018: Nano Convergence
C Gil, J Dorca-Arévalo, J Blasi
Epsilon toxin (Etx) from Clostridium perfringens is synthesized as a very low-active prototoxin form (proEtx) that becomes active upon proteolytic activation and has the capacity to cross the blood-brain barrier (BBB), thereby producing severe neurological effects. The identity and requirements of host receptors of Etx remain a matter of controversy. In the present study, we analysed the binding of proEtx or Etx to liposomes containing distearoylphosphatidylcholine (DSPC), cholesterol and sulfatide, or alternatively to detergent-solubilized lipids, using surface plasmon resonance (SPR)...
January 2019: Biochimica et biophysica acta. Biomembranes
Yang Hu, Pieter J Gaillard, Jaap Rip, Elizabeth C M de Lange, Margareta Hammarlund-Udenaes
Despite the promising features of liposomes as brain drug delivery vehicles, it remains uncertain how they influence the brain uptake in vivo. In order to gain a better fundamental understanding of the interaction between liposomes and the blood-brain barrier (BBB), it is indispensable to test if liposomes affect drugs with different BBB transport properties (active influx or efflux) differently. The aim of this study was to quantitatively evaluate how PEGylated (PEG) liposomes influence brain delivery of diphenhydramine (DPH), a drug with active influx at the BBB, in rats...
November 8, 2018: Molecular Pharmaceutics
Chao Zhang, Wei Feng, Elena Vodovozova, Daria Tretiakova, Ivan Boldyrevd, Yusha Li, Jurgen Kürths, Tingting Yu, Oxana Semyachkina-Glushkovskaya, Dan Zhu
The photodynamic (PD) effect has been reported to be efficient for the opening of the blood-brain barrier (BBB), which provides a new informative platform for developing perspective strategies towards brain disease therapy and drug delivery. However, this method is usually performed via craniotomy due to high scattering of the turbid skull. In this work, we employed a newly-developed optical clearing skull window for investigating non-invasive PD-induced BBB opening to high weight molecules and 100-nm fluid-phase liposomes containing ganglioside GM1...
October 1, 2018: Biomedical Optics Express
Ying Fan, Min Chen, Jinqiang Zhang, Philippe Maincent, Xuefeng Xia, Wen Wu
Intranasal drug delivery is emerging as a reliable and promising pathway to deliver a wide range of therapeutic agents including small and large molecules, peptides and proteins, genes to the central nervous system for the treatment of brain diseases such as Alzheimer's disease, Parkinson's disease, depression, migraine, schizophrenia, and glioma. This presents noninvasive entry into the brain via direct nose-to-brain and/or indirect nose-to-blood-to-brain routes. Several nanocarrier-based strategies have been developed to transport therapeutic agents to the brain including nanoparticles, liposomes, and exosomes following intranasal delivery...
2018: Critical Reviews in Therapeutic Drug Carrier Systems
Abdur Rauf Khan, Xiaoye Yang, Manfei Fu, Guangxi Zhai
Most of the potential therapeutic agents capable to modulate the pathophysiology or treat the neurological disorders and brain tumors are useless in the current modern and advanced era of neuroscience due to the impeding action of biological barriers. Among various therapeutic strategies applied for translocation of drug delivery across the blood-brain barrier (BBB), nanoformulations set an excellent platform for brain targeting by overcoming the biological and chemical barriers and protecting drug from efflux to promote the optimum therapeutic drug concentration in brain parenchyma tissues...
December 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Iason Papademetriou, Else Vedula, Joseph Charest, Tyrone Porter
The blood-brain barrier (BBB) limits transport of nanoparticles from the circulation to the brain parenchyma. Angiopep-2, a peptide which functions as a brain transport vector, can be coupled to nanoparticles in order to facilitate binding and internalization by brain endothelial cells (ECs), and subsequent BBB penetration. This multi-step process may be affected by blood flow over brain ECs, as flow influences endothelial cell phenotype as well as interactions of nanoparticles with ECs. In the present study a microfluidic BBB model was constructed to evaluate binding and internalization by brain ECs, as well as BBB penetration of Angiopep-2 coupled liposomes (Ang2-Liposomes) in static and flow conditions...
2018: PloS One
Sushant Lakkadwala, Jagdish Singh
Glioma is a highly malignant tumor that starts in the glial cells of brain. Tumor cells reproduce quickly and infiltrate rapidly in high grade glioma. Permeability of chemotherapeutic agents into brain is restricted owing to the presence of blood brain barrier (BBB). In this study, we developed a dual functionalized liposomal delivery system for efficient transport of chemotherapeutics across BBB for the treatment of glioma. Liposomes were surface modified with transferrin (Tf) for receptor targeting, and cell penetrating peptide PFVYLI (PFV) to increase translocation of doxorubicin (Dox) and Erlotinib (Erlo) across the BBB into glioblastoma (U87) tumor cells...
September 21, 2018: Colloids and Surfaces. B, Biointerfaces
Annarita Falanga, Giuseppina Iachetta, Lucia Lombardi, Emiliana Perillo, Assunta Lombardi, Giancarlo Morelli, Salvatore Valiante, Stefania Galdiero
We have investigated the crossing of the blood brain barrier (BBB) by the peptide gH625 and compared to the uptake by liver in vivo. We clearly observed that in vivo administration of gH625 allows the crossing of the BBB, although part of the peptide is sequestered by the liver. Furthermore, we used a combination of biophysical techniques to gain insight into the mechanism of interaction with model membranes mimicking the BBB and the liver. We observed a stronger interaction for membranes mimicking the BBB where gH625 clearly undergoes a change in secondary structure, indicating the key role of the structural change in the uptake mechanism...
September 14, 2018: Scientific Reports
N Poovaiah, Z Davoudi, H Peng, B Schlichtmann, S Mallapragada, B Narasimhan, Q Wang
Neurodegenerative diseases refer to disorders of the central nervous system (CNS) that are caused by neuronal degradations, dysfunctions, or death. Alzheimer's disease, Parkinson's disease, and Huntington's disease (APHD) are regarded as the three major neurodegenerative diseases. There is a vast body of literature on the causes and treatments of these neurodegenerative diseases. However, the main obstacle in developing an effective treatment strategy is the permeability of the treatment components at the blood-brain barrier (BBB)...
September 20, 2018: Nanoscale
Vieri Piazzini, Elisa Landucci, Giulia Graverini, Domenico E Pellegrini-Giampietro, Anna Rita Bilia, Maria Camilla Bergonzi
(1) Background: Andrographolide (AG) is a natural compound effective for the treatment of inflammation-mediated neurodegenerative disorders. The aim of this investigation was the preparation of liposomes to enhance the penetration into the brain of AG, by modifying the surface of the liposomes by adding Tween 80 (LPs-AG) alone or in combination with Didecyldimethylammonium bromide (DDAB) (CLPs-AG). (2) Methods: LPs-AG and CLPs-AG were physically and chemically characterized. The ability of liposomes to increase the permeability of AG was evaluated by artificial membranes (PAMPA) and hCMEC/D3 cells...
August 13, 2018: Pharmaceutics
Khwaja Salahuddin Siddiqi, Azamal Husen, Sayed Sartaj Sohrab, Mensur Osman Yassin
Nanomaterials (NMs) are receiving remarkable attention due to their unique properties and structure. They vary from atoms and molecules along with those of bulk materials. They can be engineered to act as drug delivery vehicles to cross blood-brain barriers (BBBs) and utilized with better efficacy and safety to deliver specific molecules into targeted cells as compared to conventional system for neurological disorders. Depending on their properties, various metal chelators, gold nanoparticles (NPs), micelles, quantum dots, polymeric NPs, liposomes, solid lipid NPs, microparticles, carbon nanotubes, and fullerenes have been utilized for various purposes including the improvement of drug delivery system, treatment response assessment, diagnosis at early stage, and management of neurological disorder by using neuro-engineering...
August 10, 2018: Nanoscale Research Letters
Tatiana N Pashirova, Irina V Zueva, Konstantin A Petrov, Svetlana S Lukashenko, Irek R Nizameev, Natalya V Kulik, Aleksandra D Voloshina, Laszlo Almasy, Marsil K Kadirov, Patrick Masson, Eliana B Souto, Lucia Ya Zakharova, Oleg G Sinyashin
New mixed cationic liposomes based on L-α-phosphatidylcholine and dihexadecylmethylhydroxyethylammonium bromide (DHDHAB) were designed to overcome the BBB crossing by using the intranasal route. Synthesis and self-assembly of DHDHAB were performed. A low critical association concentration (0.01 mM), good solubilization properties toward hydrophobic dye Orange OT and antimicrobial activity against gram-positive bacteria Staphylococcus aureus (MIC=7.8 μg mL-1 ) and Bacillus cereus (MIC=7.8 μg mL-1 ), low hemolytic activities against human red blood cells (less than 10%) were achieved...
November 1, 2018: Colloids and Surfaces. B, Biointerfaces
Sushant Lakkadwala, Jagdish Singh
Drug delivery to the brain has been a major challenge due to the presence of the blood-brain barrier, which limits the uptake of most chemotherapeutics into brain. We developed a dual-functionalized liposomal delivery system, conjugating cell penetrating peptide penetratin to transferrin-liposomes (Tf-Pen-conjugated liposomes) to enhance the transport of an anticancer chemotherapeutic drug, 5-fluorouracil (5-FU), across the blood-brain barrier into the tumor cells. The in vitro cellular uptake study showed that the dual-functionalized liposomes are capable of higher cellular uptake in glioblastoma (U87) and brain endothelial (bEnd...
November 2018: Journal of Pharmaceutical Sciences
Jianlou Niu, Junjun Xie, Kaiwen Guo, Xiaomin Zhang, Feng Xia, Xinyu Zhao, Lintao Song, Deli Zhuge, Xiaokun Li, Yingzheng Zhao, Zhifeng Huang
Fibroblast growth factor-20 (FGF20) is a paracrine member of the FGF family that is preferentially expressed in the substantia nigra pars compacta (SNpc). Previous studies have demonstrated that FGF20 enhances the survival of dopaminergic neurons suggesting the potential use of FGF20 to treat Parkinson's disease (PD). However, the reduced solubility of the bacterial recombinant human FGF20 (rhFGF20) and the absence of efficient strategies to transport rhFGF20 across the blood-brain barrier (BBB) have halted its clinical application...
November 2018: Drug Delivery
Lorena F Fernandes, Gisele E Bruch, André R Massensini, Frédéric Frézard
The complexity of the central nervous system (CNS), its limited self-repairing capacity and the ineffective delivery of most CNS drugs to the brain contribute to the irreversible and progressive nature of many neurological diseases and also the severity of the outcome. Therefore, neurological disorders belong to the group of pathologies with the greatest need of new technologies for diagnostics and therapeutics. In this scenario, nanotechnology has emerged with innovative and promising biomaterials and tools...
2018: Frontiers in Neuroscience
Antonietta Arcella, Sara Palchetti, Luca Digiacomo, Daniela Pozzi, Anna Laura Capriotti, Luigi Frati, Maria Antonietta Oliva, Georgia Tsaouli, Rossella Rota, Isabella Screpanti, Morteza Mahmoudi, Giulio Caracciolo
Temozolomide (TMZ) is the current first-line chemotherapy for treatment of glioblastoma multiforme (GBM). However, similar to other brain therapeutic compounds, access of TMZ to brain tumors is impaired by the blood-brain barrier (BBB) leading to poor response for GBM patients. To overcome this major hurdle, we have synthesized a set of TMZ-encapsulating nanomedicines made of four cationic liposome (CL) formulations with systematic changes in lipid composition and physical-chemical properties. The targeting nature of this nanomedicine is provided by the recruitment of proteins, with natural targeting capacity, in the biomolecular corona (BC) layer that forms around CLs after exposure to human plasma (HP)...
July 31, 2018: ACS Chemical Neuroscience
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