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peptide drug delivery

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https://www.readbyqxmd.com/read/28108572/use-of-ldl-receptor-targeting-peptide-vectors-for-in-vitro-and-in-vivo-cargo-transport-across-the-blood-brain-barrier
#1
Yves Molino, Marion David, Karine Varini, Françoise Jabès, Nicolas Gaudin, Aude Fortoul, Karima Bakloul, Maxime Masse, Anne Bernard, Lucile Drobecq, Pascaline Lécorché, Jamal Temsamani, Guillaume Jacquot, Michel Khrestchatisky
The blood-brain barrier (BBB) prevents the entry of many drugs into the brain and, thus, is a major obstacle in the treatment of CNS diseases. There is some evidence that the LDL receptor (LDLR) is expressed at the BBB and may participate in the transport of endogenous ligands from blood to brain, a process referred to as receptor-mediated transcytosis. We previously described a family of peptide vectors that were developed to target the LDLR. In the present study, in vitro BBB models that were derived from either wild-type and LDLR knockout animals (ldlr(-/-)) were used to validate the specific LDLR-dependent transcytosis of LDL via a nondegradative route...
January 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28108360/archaeal-lipids-in-oral-delivery-of-therapeutic-peptides
#2
Ann-Christin Jacobsen, Sara M Jensen, Gert Fricker, Martin Brandl, Alexander Treusch
Archaea contain membrane lipids that differ from those found in the other domains of life (Eukarya and Bacteria). These lipids consist of isoprenoid chains attached via ether bonds to the glycerol carbons at the sn-2,3 positions. Two types of ether lipids are known, polar diether lipids and bipolar tetraether lipids. The inherent chemical stability and unique membrane-spanning characteristics of tetraether lipids render them interesting for oral drug delivery purposes. Archaeal lipids form liposomes spontaneously (archaeosomes) and may be incorporated in conventional liposomes (mixed vesicles)...
January 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28107705/incorporation-of-antimicrobial-peptides-in-nanostructured-lipid-membrane-mimetic-bilayer-cubosomes
#3
Thomas G Meikle, Alexandru Zabara, Lynne J Waddington, Frances Separovic, Calum J Drummond, Charlotte E Conn
The inverse bicontinuous lipidic cubic phase offers a simple and robust membrane mimetic with the ability to encapsulate peptides, potentially increasing bioavailability, while also offering a platform from which functionalized, targeted nanoparticles can be developed. Herein we have investigated the use of a number of cubic phase nanoparticle systems with encapsulated antimicrobial peptides gramicidin A', melittin, and alamethicin. The optimal peptide loading ranges, over which cubic symmetry was retained, were determined using small angle X-ray scattering...
January 8, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28105728/invention-of-stimulus-responsive-peptide-bond-cleaving-residue-spr-and-its-application-to-chemical-biology-tools
#4
Akira Shigenaga, Jun Yamamoto, Taiki Kohiki, Tsubasa Inokuma, Akira Otaka
Elucidation of biological functions of peptides and proteins is essential for understanding peptide/protein-related biological events and developing drugs. Caged peptides and proteins that release a parent active peptide/protein by photo-irradiation have successfully been employed to elucidate the functions. Whereas the usual caged peptide/protein enables conversion of an inactive form to an active form (OFF-to-ON conversion) by photo-induced deprotection, photo-triggered main chain cleavage is reported to be applicable to ON-to-OFF conversion...
January 19, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28105163/selection-of-antitumor-displayed-peptides-for-the-specific-delivery-of-the-anticancer-drug-lactaptin
#5
Anna Andreevna Nemudraya, Elena Vladimirovna Kuligina, Alexandr Alexeevich Ilyichev, Alexandr Sergeevich Fomin, Grigory Alexandrovich Stepanov, Anna Valentinovna Savelyeva, Olga Alexandrovna Koval, Vladimir Alexandrovich Richter
It has been previously demonstrated that lactaptin, the proteolytic fragment of human milk protein κ-casein, induces the death of various cultured cancer cells. The recombinant analog of lactaptin, RL2, effectively induces the apoptosis of mouse hepatocarcinoma-1 (HA-1) tumor cells in vitro and suppress the growth of HA-1 tumors and metastases in vivo. The antitumor drug Lactaptin developed on the basis of RL2 has been successful in preclinical trials. Lactaptin shows its efficiency in relation to mouse and human cancer cells and tumors...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101766/crossing-the-blood-brain-barrier-recent-advances-in-drug-delivery-to-the-brain
#6
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/28096156/bacterial-derived-cell-penetrating-peptides-deliver-gentamicin-to-kill-intracellular-pathogens
#7
Marta Gomarasca, Thaynan F C Martins, Lilo Greune, Philip R Hardwidge, M Alexander Schmidt, Christian Rüter
Commonly used antimicrobials show poor cellular uptake and often have limited access to intracellular targets, resulting in low antimicrobial activity against intracellular pathogens. An efficient delivery system to transport these drugs to the intracellular site of action is needed. Cell-penetrating peptides (CPPs) mediate the internalization of biologically active molecules into the cytoplasm. Here we characterized two CPPs, α1H and α2H, derived from the Y. enterocolitica YopM effector protein. These CPPs, as well as Tat(Trans-activator of transcription) from HIV-1 virus, were used to deliver the antibiotic gentamicin to target intracellular bacteria...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28094952/effect-of-an-enhanced-nose-to-brain-delivery-of-insulin-on-mild-and-progressive-memory-loss-in-the-senescence-accelerated-mouse
#8
Noriyasu Kamei, Misa Tanaka, Hayoung Choi, Nobuyuki Okada, Takamasa Ikeda, Rei Itokazu, Mariko Takeda-Morishita
Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28090777/biodegradable-neuro-compatible-peptide-hydrogel-promotes-neurite-outgrowth-shows-significant-neuroprotection-and-delivers-anti-alzheimer-drug
#9
Anindyasundar Adak, Gaurav Das, Surajit Barman, Saswat Mohapatra, Debmalya Bhunia, Batakrishna Jana, Surajit Ghosh
A novel neuro-compatible peptide based hydrogel has been designed and developed, which contains microtubule stabilizing and neuroprotective short peptide. This hydrogel shows strong three dimensional cross-linked fibrillary networks, which can capture water molecules. Interestingly, this hydrogel serves as excellent biocompatible soft-material for 2D and 3D (neuro-sphere) neuron cell culture and provides stability of key cytoskeleton filaments such as microtubule and actin. Remarkably, it was observed that this hydrogel slowly enzymatically degrades and releases neuroprotective peptide, which promotes neurite outgrowth of neuron cell as well as exhibits excellent neuroprotection against anti-NGF induced toxicity in neuron cells...
January 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28088635/mucoadhesive-amorphous-solid-dispersions-for-sustained-release-of-poorly-water-soluble-drugs
#10
Justin S LaFountaine, Leena Kumari Prasad, Dave A Miller, James W McGinity, Robert O Williams
The oral delivery of mucoadhesive patches has been shown to enhance the absorption of large molecules such as peptides. We hypothesized that this mechanism could have utility for poorly soluble small molecules by utilizing a mucoadhesive polymer as the matrix for an amorphous solid dispersion. Binary dispersions of itraconazole and carbomer (Carbopol 71G) were prepared utilizing a thermokinetic mixing process (KinetiSol Dispersing) and the physicochemical properties were investigated by powder x-ray diffraction, calorimetry, and liquid chromatography...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28088076/in%C3%A2-vivo-visualization-of-endogenous-mir-21-using-hyaluronic-acid-coated-graphene-oxide-for-targeted-cancer-therapy
#11
Do Won Hwang, Han Young Kim, Fangyuan Li, Ji Yong Park, Dohyun Kim, Jae Hyung Park, Hwa Seung Han, Jung Woo Byun, Yun-Sang Lee, Jae Min Jeong, Kookheon Char, Dong Soo Lee
Oncogene-targeted nucleic acid therapy has been spotlighted as a new paradigm for cancer therapeutics. However, in vivo delivery issues and uncertainty of therapeutic antisense drug reactions remain critical hurdles for a successful targeted cancer therapy. In this study, we developed a fluorescence-switchable theranostic nanoplatform using hyaluronic acid (HA)-conjugated graphene oxide (GO), which is capable of both sensing oncogenic miR-21 and inhibiting its tumorigenicity simultaneously. Cy3-labeled antisense miR-21 peptide nucleic acid (PNA) probes loaded onto HA-GO (HGP21) specifically targeted CD44-positive MBA-MB231 cells and showed fluorescence recovery by interacting with endogenous miR-21 in the cytoplasm of the MBA-MB231 cells...
December 31, 2016: Biomaterials
https://www.readbyqxmd.com/read/28087353/thiolated-polymers-as-mucoadhesive-drug-delivery-systems
#12
REVIEW
Sarah Duggan, Wayne Cummins, Orla O' Donovan, Helen Hughes, Eleanor Owens
Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug...
January 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28079225/bioconjugation-strategies-to-couple-supramolecular-exo-functionalized-palladium-cages-to-peptides-for-biomedical-applications
#13
J Han, A Schmidt, T Zhang, H Permentier, G M M Groothuis, R Bischoff, F E Kühn, P Horvatovich, A Casini
Supramolecular Pd2L4 cages (L = ligand) hold promise as drug delivery systems. With the idea of achieving targeted delivery of the metallacages to tumor cells, the bioconjugation of exo-functionalized self-assembled Pd2L4 cages to peptides following two different approaches is reported for the first time. The obtained bioconjugates were analyzed and identified by high-resolution mass spectrometry.
January 12, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28075559/one-component-supramolecular-filament-hydrogels-as-theranostic-label-free-magnetic-resonance-imaging-agents
#14
Lye Lin Lock, Yuguo Li, Xinpei Mao, Hanwei Chen, Verena Staedtke, Renyuan Bai, Wang Ma, Ran Lin, Yi Li, Guanshu Liu, Honggang Cui
Gadolinium (Gd)-based compounds and materials are the most commonly used magnetic resonance imaging (MRI) contrast agents in the clinic; however, safety concerns associated with their toxicities in the free ionic form have promoted the development of new generations of metal-free contrast agents. Here we report a supramolecular strategy to convert an FDA-approved anticancer drug, Pemetrexed (Pem), to a molecular hydrogelator with inherent chemical exchange saturation transfer (CEST) MRI signals. The rationally designed drug-peptide conjugate can spontaneously associate into filamentous assemblies under physiological conditions and consequently form theranostic supramolecular hydrogels for injectable delivery...
January 11, 2017: ACS Nano
https://www.readbyqxmd.com/read/28069504/ph-sensitive-peptide-hydrogel-for-glucose-responsive-insulin-delivery
#15
Xue Li, Mian Fu, Jun Wu, Chenyu Zhang, Xin Deng, Arvind Dhinakar, Wenlong Huang, Hai Qian, Liang Ge
: Glucose-responsive system is one of important options for self-regulated insulin delivery to treat diabetes, which has become an issue of great public health concern in the world. In this study, we developed a novel and biocompatible glucose-responsive insulin delivery system using a pH-sensitive peptide hydrogel as a carrier loaded with glucose oxidase, catalase and insulin. The peptide could self-assemble into hydrogel under physiological conditions. When hypoglycemia is encountered, neighboring alkaline amino acid side chains are significantly repulsed due to reduced local pH by the enzymatic conversion of glucose into glucoinc acid...
January 6, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28068767/microneedle-assisted-skin-permeation-by-non-toxic-bioengineerable-gas-vesicle-nanoparticles
#16
Abhay U Andar, Ram Karan, Wolf T Pecher, Priya DasSarma, William D Hedrich, Audra L Stinchcomb, Shiladitya DasSarma
Gas vesicle nanoparticles (GVNPs) are hollow, buoyant protein organelles produced by the extremophilic microbe Halobacterium sp. NRC-1 and are being developed as bioengineerable and biocompatible antigen and drug-delivery systems (DDS). Dynamic light scattering measurements of purified GVNP suspensions showed a mean diameter of 245 nm. In vitro diffusion studies using Yucatan miniature pig skin showed GVNP permeation to be enhanced after MN-treatment compared to untreated skin. GVNPs were found to be non-toxic to mammalian cells (human kidney and rat mycocardial myoblasts)...
January 9, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28068466/controlling-self-assembling-peptide-hydrogel-properties-through-network-topology
#17
Jie Gao, Claire Tang, Andrew M Smith, Aline Fiona Miller, Alberto Saiani
Self-assembling peptide based hydrogels have encountered increasing interest in the recent years as scaffolds for 3D cell culture or for controlled drug delivery. One of the main challenges is the fine control of the mechanical properties of these materials. The bulk properties of hydrogel not only depend on the intrinsic properties of the fibres but also on the network topology formed. In this work we show how fibre-fibre interactions can be manipulated by design to control the final hydrogels network topology and therefore control the final properties of the material...
January 9, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28066811/ph-dependent-cellular-internalization-of-paramagnetic-nanoparticle
#18
Branislava Janic, Mohammed Pi Bhuiyan, James R Ewing, Meser M Ali
A hallmark of the tumor microenvironment in malignant tumor is extracellular acidosis, which can be exploited for targeted delivery of drugs and imaging agents. A pH sensitive paramagnetic nanoaparticle (NP) is developed by incorporating GdDOTA-4AmP MRI contrast agent and pHLIP (pH Low Insertion Peptide) into the surface of a G5-PAMAM dendrimer. pHLIP showed pH-selective insertion and folding into cell membranes, but only in acidic conditions. We demonstrated that pHLIP-conjugated Gd44-G5 paramagnetic nanoparticle binds and fuses with cellular membrane at low pH, but not at normal physiological pH, and that it promotes cellular uptake...
August 26, 2016: ACS Sensors
https://www.readbyqxmd.com/read/28065935/two-birds-one-stone-dual-targeting-of-the-cancer-cell-surface-and-subcellular-mitochondria-by-the-galectin-3-binding-peptide-g3-c12
#19
Wei Sun, Lian Li, Qing-Qing Yang, Zhi-Rong Zhang, Yuan Huang
Active tumor-targeting approaches using specific ligands have drawn considerable attention over the years. However, a single ligand often fails to simultaneously target the cancer cell surface and subcellular organelles, which limits the maximum therapeutic efficacy of delivered drugs. We describe a polymeric delivery system modified with the G3-C12 peptide for sequential dual targeting. In this study, galectin-3-targeted G3-C12 peptide was conjugated onto the N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer for the delivery of D(KLAKLAK)2 (KLA) peptide...
January 9, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28060268/a-facile-and-efficient-approach-for-the-production-of-reversible-disulfide-cross-linked-micelles
#20
Yuanpei Li, Gaurav Bharadwaj, Joyce S Lee
Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. Improving drug delivery to maximize therapeutic outcomes and to reduce drug-associated side effects are some of the cornerstones of present-day nanomedicine. Nanoparticles in particular have found a wide application in cancer treatment. Nanoparticles that offer a high degree of flexibility in design, application, and production based on the tumor microenvironment are projected to be more effective with rapid translation into clinical practice...
December 23, 2016: Journal of Visualized Experiments: JoVE
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