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peptide drug delivery

Amrita Kadari, Deep Pooja, Ravuri Halley Gora, Sagarika Gudem, Venkata Ramana Murthy Kolapalli, Hitesh Kulhari, Ramakrishna Sistla
Glioblastoma multiforme (GBM) is one of the most encountered gliomas of the central nervous system. The chemotherapeutic drugs used in the treatment of GBM suffer from poor blood brain barrier penetration, severe systemic toxicities and lack of specificity towards tumor cells. There is an urgent need to explore novel drug delivery systems specifically designed for targeting GBM. Solid lipid nanoparticles (SLN) are biocompatible vehicle with less toxicity issues compared to other drug delivery systems and serve the purpose of obviating the limitations posed by existing anti-cancer drugs for GBM...
September 20, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Yanyu Zhang, Li Zhang, Yang Hu, Kuan Jiang, Zhuoquan Li, Yao-Zhong Lin, Gang Wei, Weiyue Lu
Application of liposomes-based drug delivery in treatment of glioma has been hampered by the poor permeability of blood-brain barrier and the low uptake efficiency by glioma tissues. Moreover, many chemotherapy drugs promote the activation of the NF-κB, which plays a role in the development and progression of cancer and chemoresistance. In this report, CB5005 peptide, designed for its dual function in cell membrane penetration and NF-κB inhibition, was conjugated to PEGylated liposomes loaded with doxorubicin (CB5005-LS/DOX) or a fluorescent dye (CB5005-LS/dye)...
September 19, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ning-Hui Lu, Su-Chun How, Chien-Yu Lin, Shen-Long Tsai, Zuzana Bednarikova, Diana Fedunova, Zuzana Gazova, Josephine W Wu, Steven S-S Wang
More than thirty human proteins and/or peptides can aggregate to form amyloid deposits that are linked to several amyloid diseases including clinical syndrome injection-localized amyloidosis, which is correlated with the aggregation of the 51-residue polypeptide insulin. While no cure is currently available toward tackling amyloid diseases, prevention or suppression of amyloid fibrillization is considered as the primary therapeutic strategy. Nanomaterials have been demonstrated to possess great potential in the fields of biomedical diagnosis and drug delivery, they are also able to affect the amyloid aggregation of proteins...
September 14, 2018: Colloids and Surfaces. B, Biointerfaces
Anna Florczak, Katarzyna Jastrzebska, Wojciech Bialas, Andrzej Mackiewicz, Hanna Dams-Kozlowska
Bioengineered spider silk is a focus of research due to its biocompatibility, biodegradability, and excellent mechanical properties. Functionalized silk can be processed into spheres and employed as selective drug delivery vehicles in targeted cancer treatment. Efficient, repeatable and controllable processing conditions are essential to drug carrier development. This study aimed to optimize the processing conditions of silk spheres formation, scale-up, and automation of the silk spheres production process...
September 22, 2018: Journal of Biomedical Materials Research. Part A
Matthew R Aronson, Andrew W Simonson, Lindsey M Orchard, Manuel Llinás, Scott H Medina
Anticancer peptides (ACPs) are cationic amphiphiles that preferentially kill cancer cells through folding-dependent membrane disruption. Although ACPs represent attractive therapeutic candidates, particularly against drug-resistant cancers, their successful translation into clinical practice has gone unrealized due to their poor bioavailability, serum instability and, most importantly, severe hemolytic toxicity. Here, we exploit the membrane-specific interactions of ACPs to prepare a new class of peptide-lipid particle, we term a lipopeptisome (LP)...
September 18, 2018: Acta Biomaterialia
Weijun Gui, Christine A Ott, Kun Yang, Jedidiah S Chung, Siqi Shen, Zhihao Zhuang
Advancement in our knowledge of deubiquitinases (DUBs) and their biological functions requires biochemical tools permitting interrogation of DUB activities under physiologically relevant conditions. Activity-based DUB probes (DUB ABPs) have been widely used in investigating the function and activity of DUBs. However, most ubiquitin (Ub)-based DUB ABPs are not cell-permeable, limiting their utility to purified proteins and cell lysates. Lysis of cells usually leads to dilution of the cytoplasm and disruption of the normal cellular organization, which may alter the activity of many DUBs and DUB complexes...
September 21, 2018: Journal of the American Chemical Society
Kate J F Carnevale, Megan E Muroski, Parth Nalin Vakil, Megan E Foley, Geoffry Laufersky, Rachael Kenworthy, Diego A R Zorio, Thomas J Morgan, Cathy W Levenson, Geoffrey F Strouse
Research over the past decade has identified several of the key limiting features in multidrug resistance (MDR) cancer ther-apy applications, such as evolving glycoprotein receptors at the surface of the cell that limit therapeutic uptake, metabolic changes leading to protection from multidrug resistant mediators by enhanced degradation or efflux of therapeutics, and difficulty ensuring retention of intact and functional drugs once endocytosed. Nanoparticles have been demonstrated to be effective delivery vehicles for a plethora of therapeutic agents and, in the case of nucleic acid-based agents, they provide protective advantages...
September 21, 2018: Bioconjugate Chemistry
Alexandru Cǎlin, Mihai Stancu, Ana-Maria Zagrean, John G R Jefferys, Andrei S Ilie, Colin J Akerman
Current anti-epileptic medications that boost synaptic inhibition are effective in reducing several types of epileptic seizure activity. Nevertheless, these drugs can generate significant side-effects and even paradoxical responses due to the broad nature of their action. Recently developed chemogenetic techniques provide the opportunity to pharmacologically recruit endogenous inhibitory mechanisms in a selective and circuit-specific manner. Here, we use chemogenetics to assess the potential of suppressing epileptiform activity by enhancing the synaptic output from three major interneuron populations in the rodent hippocampus: parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) expressing interneurons...
2018: Frontiers in Cellular Neuroscience
Ghullam Reza Barbari, Farid Dorkoosh, Mohsen Amini, Nika Bahari Javan, Mohammad Sharifzadeh, Fateme Atyabi, Saeed Balalaie, Niyousha Rafiee Tehrani, Morteza Rafiee Tehrani
Background: Despite years of experience and rigorous research, injectable insulin is the sole trusted treatment method to control the blood glucose level in diabetes type 1 patients, but injection of insulin is painful and poses a lot of stress to the patients, especially children, therefore, development of a non-injectable formulation of insulin is a major breakthrough in the history of medicine and pharmaceutical sciences. Methods: In this study, a novel peptide grafted derivative of chitosan (CPP-g- chitosan) is synthesized and its potential for oral delivery of proteins and peptides is evaluated...
2018: International Journal of Nanomedicine
Kun Nie, Qi An, Jeffrey I Zink, Xiang Yu, Yihe Zhang
The layer-by-layer technique was exploited to adjust the magnitude of the host⁻guest interactions between adamantane and cyclodextrin. The effect depends on numerous complex and changeable growth profiles of the films and the number of bilayers. These composite films of mesoporous silica nanoparticles and hyaluronic acid⁻cyclodextrin(HA-CD) were constructed to load the fluorescent dyes and peptides. The release rates of these molecules would decrease with an increase in the number of layers. A laser scanning confocal microscope was utilized to obtain the diffusion coefficient of fluorescein isothiocyanate...
September 17, 2018: Materials
Miko Yamada, Hossam Tayeb, Hequn Wang, Nhung Dang, Yousuf H Mohammed, Sam Osseiran, Paul J Belt, Michael S Roberts, Conor L Evans, Frank Sainsbury, Tarl W Prow
This study demonstrates, for the first time, clinical testing of elongated silica microparticles (EMP) combined with tailorable nanoemulsions (TNE) to enhance topical delivery of hydrophobic drug surrogates. Likewise, this is the first report of 6-carboxyfluorescein (a model molecule for topically delivered hydrophobic drugs) AM1 & DAMP4 (novel short peptide surfactants) used in volunteers. The EMP penetrates through the epidermis and stop at the dermal-epidermal junction (DEJ). TNE are unusually stable and useful because the oil core allows high drug loading levels and the surface properties can be easily controlled...
September 15, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Bowen Li, Fei Wang, Lijuan Gui, Qing He, Yuxin Yao, Haiyan Chen
In past decades, rapid progress in nanoparticle (NP) synthesis and engineering has provided a broad range of nanoscale agents affording both therapeutic and diagnostic functions. More recently, the emergence of biomimetic NPs as an efficient and promising technology has further expanded this field. The employment of biomemetic NPs offers many distinct advantages, including enhanced stability, the solubilization of hydrophobic payloads, extended blood residence times and the ability to better target a region of interest...
September 18, 2018: Nanomedicine
Sheng Lu, Feng Zhao, Qiuxin Zhang, P Chen
Despite the great progress in the field of drug delivery systems for cancer treatment over the last decade, many challenges still lie ahead, such as low drug loading, deep penetration of tumors, side effects, and the development of drug resistance. A class of cationic membrane lytic peptides has shown potential as an anticancer agent by inducing cancer cell death via membrane disruption; meanwhile, their intrinsic selectivity renders them as having low cytotoxicity towards noncancerous cells. Here, we report the use of a cationic peptide amphiphile (PA), named PAH6, to load doxorubicin (Dox) that is intercalated in an ATP-binding aptamer-incorporated DNA scaffold...
September 14, 2018: International Journal of Molecular Sciences
Reza Mahjub, Sukhdeep Jatana, Suen Ern Lee, Zhu Qin, Griffin Pauli, Meysam Soleimani, Soheil Madadi, Shyh-Dar Li
Cancer immunotherapy aimed at boosting cancer-specific immunoresponses to eradicate tumor cells has evolved as a new treatment modality. Nanoparticles incorporating antigens and immunomodulatory agents can activate immune cells and modulate the tumor microenvironment to enhance antitumor immunity. The nanotechnology approach has been demonstrated to be superior to standard formulations in in-vivo settings. In this article, we focus on recent advances made within the last 5 years in nanoparticle-based cancer immunotherapy, including peptide- and nucleic acid-based nanovaccines, nanomedicines containing an immunoadjuvant to activate antitumor immunity, nanoparticle delivery of immune checkpoint inhibitors and the combination of the above approaches...
September 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Monessha Nambiar, Li-Sheng Wang, Vincent M Rotello, Jean Chmielewski
We report a set of coiled-coil peptides, radially functionalized with bipyridines, that demonstrate hierarchical assembly into banded rectangular nano- and microstructures, the dimensions of which vary with the strategic placement and number of aromatic groups on the monomer backbone. Finer structural aspects of the hexagonal packing of the individual trimers was determined by X-ray scattering, including inter-trimer aromatic interactions between bipyridine moieties. The ease of formation of these biomaterials under physiological conditions and the use of pH to reversibly modulate assembly demonstrate future potential for a range of biological applications, such as drug delivery in a pH-controlled manner...
September 17, 2018: Journal of the American Chemical Society
Jordan Bouilloux, Oleksandr Yuschenko, Bogdan Dereka, Gianluca Boso, Andréj Babič, Hugo Zbinden, Eric Vauthey, Norbert Lange
Previously, we have shown that the use of a cyclopeptidic carrier could be of great interest for the design of fully characterized prodrugs for further use in photodynamic therapy. In order to further optimize the design, we decided to modify the highly quenched conjugate uPA-cPPP4/5 by co-loading a long-distance fluorescence quencher. For this purpose we tethered two black hole quenchers (BHQ3) together with two pheophorbide A moities onto the same PEGylated backbone and assessed the modified photophysical properties...
September 14, 2018: Photochemical & Photobiological Sciences
Xiuran Niu, Zhihui Gao, Shanshan Qi, Linjia Su, Nan Yang, Xiuli Luan, Jia Li, Qing Zhang, Yingli An, Sihe Zhang
Background: Successful implementation of gene therapy heavily relies on efficiently delivering genetic materials and specific targeting into cells. Oncogene-driven endocytosis stimulates nutrient uptake and also develops an endocytosis-mediated defense against therapeutic agents. Cell-penetrating peptides, typically HIV-Tat, are well known for efficient delivery of nucleic acid drugs but lack targeting specificity. Various passive targeting strategies were pursued to enhance the tumor targeting efficiency; however, they are still limited by complicated cellular endocytosis routes and the heterogeneity of cancer types...
2018: International Journal of Nanomedicine
Mena Asha Krishnan, Amit Pandit, Venkatesh Chelvam
The development of small molecule ligand-targeted therapeutics is currently of paramount importance for treatment of cancer due to their potential to reduce system toxicity and increase potency of a delivered chemotherapeutic drug. The main aim of a targeted drug-delivery technique is to release the drug cargo selectively into tumor tissues, avoiding off-site toxicity to healthy tissues and organs during chemotherapy. In this strategy, a chemotherapeutic drug is conjugated to a homing ligand, which has high affinity for proteins over-expressed on cancer cells, via a peptide linker and a self-immolative segment that facilitates intracellular release of drug cargo...
September 13, 2018: Current Protocols in Chemical Biology
Francesca Sacchetti, Gaetano Marverti, Domenico D'Arca, Leda Severi, Eleonora Maretti, Valentina Iannuccelli, Salvatore Pacifico, Glauco Ponterini, Maria Paola Costi, Eliana Leo
PURPOSE: To evaluate the potential effects of PEGylated pH-sensitive liposomes on the intracellular activity of a new peptide recently characterized as a novel inhibitor of the human thymidylate synthase (hTS) over-expressed in many drug-resistant human cancer cell lines. METHODS: Peptide-loaded pH-sensitive PEGylated (PpHL) and non-PEGylated liposomes (nPpHL) were carefully characterized and delivered to cis-platinum resistant ovarian cancer C13* cells; the influence of the PpHL on the drug intracellular activity was investigated by the Western Blot analysis of proteins involved in the pathway affected by hTS inhibition...
September 12, 2018: Pharmaceutical Research
Mengmeng Xu, Hui Zhou, Yanan Liu, Jing Sun, Wenjie Xie, Ping Zhao, Jie Liu
Alzheimer's disease (AD) has become one of the most serious societal problems globally, with no effective treatments. Parenchymal accumulation of amyloid beta (Aβ) plaques and the formation of neurofibrillary tangles are the hallmarks of AD. Their possible interactions and synergistic effects in AD have been gradually elucidated. The failure of many clinical trials suggests that it is difficult to treat AD with a focus on a single target. Instead, multiple targets may be an important direction for AD drug research...
September 19, 2018: ACS Applied Materials & Interfaces
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