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Journal of Drug Targeting

Abdel-Azim Zaghloul, Ahmad Lila, Fathy Abd-Allah, Aly Nada
BACKGROUND: Metformin hydrochloride (MtHCL) is an oral antidiabetic drug and has many other therapeutic benefits. It has poor bioavailability, narrow absorption window and extensive liver metabolism. Moreover, children and elders face difficulty to swallow the commercial oral tablets. OBJECTIVES: Preparation, in vitro/in vivo evaluation of MtHCL suppositories for rectal administration to solve some of these problems. METHODS: Suppository fatty bases (Witepsol®, Suppocire® and Massa®; different grades) and PEG bases 1000, 4000 and 6000 (different ratios), were used to prepare rectal suppository formulations each containing 500 mg drug...
January 16, 2017: Journal of Drug Targeting
Marie Iwanaga, Yukinobu Kodama, Takahiro Muro, Hiroo Nakagawa, Tomoaki Kurosaki, Kayoko Sato, Tadahiro Nakamura, Takashi Kitahara, Hitoshi Sasaki
The purpose of this study was to develop a ternary complex of plasmid DNA (pDNA) electrostatically assembled with dendrigraft poly-L-lysine (DGL) and biodegradable glycosaminoglycan for effective and secure gene delivery. High gene expression of pDNA/DGL complex was confirmed with slight cytotoxicity and erythrocyte agglutination. Anionic ternary complexes of 55.4-223.8 nm were formed by the addition of a glycosaminoglycan such as chondroitin sulfate A (CS-A), chondroitin sulfate B (CS-B), chondroitin sulfate C (CS-C), or hyaluronic acid (HA)...
January 3, 2017: Journal of Drug Targeting
Xiali Zhu, Yingjie Zhang, Heqing Huang, Huijuan Zhang, Lin Hou, Zhenzhong Zhang
Recent studies have identified that CuS nanocrystal (CuS NCs) could be used as a new class of promising photo-thermal agents due to their excellent plasmonic absorption abilities in a wide near-infrared (NIR) region. However, most of nanocarriers lack target capacity for combining chemotherapy and photothermal therapy effects. Herein, we reported chitosan (CS)-encapsulated and folic acid (FA)-modified nanoparticles (NPs) simultaneously loading with functionalized CuS NCs and docetaxel (DTX) (FA-DTX-PVP/CuS-NPs)...
December 28, 2016: Journal of Drug Targeting
Mohammad Arabpour, Robbert H Cool, Klaas Nico Faber, Wim J Quax, Hidde J Haisma
Activated hepatic stellate cells (HSCs) are known to play a central role in liver fibrosis and their elimination is a crucial step toward the resolution and reversion of liver fibrosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a molecule that may contribute to the apoptotic removal of activated HSC through binding to its dedicated receptors. In the present study, we investigated the potential application of recombinant receptor-specific TRAIL proteins in the efficient elimination of activated HSCs...
December 28, 2016: Journal of Drug Targeting
Yukako Ito, Shinji Kobuchi, Genta Inoue, Eisaku Kakumu, Miki Aoki, Toshiyuki Sakaeda, Kanji Takada
Capsaicin-loaded dissolving microneedles (DMNs) were prepared to investigate the analgesic effect of capsaicin on the skin. The dimensions of each microneedle (MN) were as follows: diameter of the basement, 17 mm; length, 500 μm; and width, 300 μm. The average capsaicin content in the DMNs loaded with a low and high dose of capsaicin was 8.8 ± 0.5 mg and 12.5 ± 0.4 mg. Almost all the capsaicin, 99.3 ± 4.1% and 99.7 ± 2.2% for low-dose and high-dose DMNs were released within 20 min...
December 14, 2016: Journal of Drug Targeting
Prashant Bhattarai, Dylan Vance, Arash Hatefi, Ban An Khaw
Drug resistance is a common phenomenon that occurs in cancer chemotherapy. Delivery of chemotherapeutic agents as polymer pro-drug conjugates (PPDCs) pretargeted with bispecific antibodies could circumvent drug resistance in cancer cells. To demonstrate this approach to overcome drug resistance, Paclitaxel (Ptxl) resistant SKOV3 TR human ovarian- and doxorubicin (Dox) resistant MCF7 ADR human mammary-carcinoma cell lines were used. Pre-targeting over-expressed biotin or HER2/neu receptors on cancer cells was conducted by biotinylated anti-DTPA or Anti-HER2/neu affibody - anti-DTPA Fab bispecific antibody complexes...
December 12, 2016: Journal of Drug Targeting
Nzungize Lambert, Abualgasim Elgaili Abdalla, Xiangke Duan, Jianping Xie
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, uses various tactics to resist on antibiotics and evade host immunity. To control tuberculosis, antibiotics with novel mechanisms of action are urgently needed. Emerging new antibiotics and underlying novel drug targets are summarized in this paper.
December 2, 2016: Journal of Drug Targeting
Yuan Xie, Anqiang Wang, Jianzhen Lin, Liangcai Wu, Haohai Zhang, Xiaobo Yang, Xueshuai Wan, Ruoyu Miao, Xinting Sang, Haitao Zhao
Monopolar spindle1 (Mps1, also known as TTK) is the core component of the spindle assembly checkpoint, which functions to ensure proper distribution of chromosomes to daughter cells. Mps1 is hardly detectable in normal organs except the testis and placenta. However, high levels of Mps1 are found in many types of human malignancies, including glioblastoma, thyroid carcinoma, breast cancer, and other cancers. Several Mps1 inhibitors can inhibit the proliferation of cancer cells and exhibit demonstrable survival benefits...
December 1, 2016: Journal of Drug Targeting
Yu-Jie Liu, Xiao-Qian Dou, Fang Wang, Jing Zhang, Xiao-Lin Wang, Gui-Li Xu, Shen-Si Xiang, Xin Gao, Jie Fu, Hai-Feng Song
Tumour immunosuppressive microenvironments inhibit antigen-specific cellular responses and interfere with CpG-mediated immunotherapy. Overcoming tumour microenvironment (TME) immunosuppression is an important strategy for effective therapy. This study investigated the ability of a tumour-targeting IL-4Rα aptamer-liposome-CpG ODN delivery system to introduce CpG into tumours and overcome the immunosuppressive TME. The IL-4Rα-liposome-CpG delivery system was prepared. FAM-CpG visualisation was used to demonstrate tumour targeting in vitro and in vivo...
December 1, 2016: Journal of Drug Targeting
Leila Rahbarnia, Safar Farajnia, Hossein Babaei, Jafar Majidi, Kamal Veisi, Vahideh Ahmadzadeh, Bahman Akbari
Phage display technology as a selection-based system is an attractive method for evolution of new biological drugs. Unique ability of phage libraries for displaying proteins on bacteriophage surfaces enable them to make a major contribution in diverse fields of researches related to the diagnosis and therapy of diseases. One of the great challenges facing researchers is the modification of phage display technology and the development of new applications. This article reviews the molecular basis of phage display library, and summarizes the novel and specific applications of this technique in the field of biological drugs development including therapeutic antibodies, peptides, vaccines, and catalytic antibodies...
November 21, 2016: Journal of Drug Targeting
Shalmali Bivalkar-Mehla, Rajeev Mehla, Ashok Chauhan
Persistent human immunodeficiency virus 1 (HIV-1) infection provokes immune activation and depletes CD4(+ )lymphocytes, leading to acquired immunodeficiency syndrome. Uninterrupted administration of combination antiretroviral therapy (cART) in HIV-infected patients suppresses viral replication to below the detectable level and partially restores the immune system. However, cART-unresponsive residual HIV-1 infection and elusive transcriptionally silent but reactivatable viral reservoirs maintain a permanent viral DNA blue print...
November 14, 2016: Journal of Drug Targeting
Min Jun Kim, Yong Hwa Hwang, Yong Hee Kim, Dong Yun Lee
Pancreatic islet transplantation is a promising treatment for treatment of type 1 diabetes; however, transplantation outcomes have been disappointing due to early graft loss that is mediated by many immune responses. Immune cells not only directly damaged islet but also produced reactive oxygen species (ROS), which is highly toxic to islet cells. Metallothionein (MT) can provide protection against oxidative stress by scavenging various range of ROS including superoxide, hydroxyl radical, hydrogen peroxide, and nitric oxide...
November 10, 2016: Journal of Drug Targeting
Maliheh Ghadiri, Paul M Young, Wolfgang Jarolimek, Georges E R Grau, Brian Oliver, Daniela Traini
The epithelial barrier in the respiratory system is a major obstacle for drug delivery to the systemic circulation both locally and systemically in the lung. Epithelial barrier hinders the transport of large macromolecules or polar drugs. Essential components of this epithelial fence are physical intercellular structures termed tight junctions. Therefore, modulating tight junctions can enhance paracellular transport across epithelial barrier. In this study, the effect of some of non-specific tight junction modulators (TJMs); (Sodium (Na) decanoate, oleic acid and ethyleneglycol-bis-(β-aminoethyl ether)-N, N'-tetraacetic acid (EGTA)) with established effect on intestinal tight junctions was evaluated for its effects on bronchial epithelial cells (Calu-3 cells)...
November 8, 2016: Journal of Drug Targeting
Irfan Ullah, Kunho Chung, Jagadish Beloor, Jongkil Kim, Minyoung Cho, Nahyun Kim, Kuen Yong Lee, Priti Kumar, Sang-Kyung Lee
siRNA entrapment within endosomes is a significant problem encountered with siRNA delivery platforms that co-opt receptor mediated entry pathways. Attachment of a cell penetrating peptide (CPP), such as nona-arginine (9R) to a cell receptor-binding ligand like the Rabies virus glycoprotein, RVG, allows effective siRNA delivery to the cytoplasm by non-endocytic pathways, but a significant amount of siRNA complexes also enters the cell by ligand-induced receptor endocytosis and remain localized in endosomes. Here, we report that the incorporation of trileucine (3 Leu) residues as an endo-osmolytic moiety in the peptide improves endosomal escape and intracellular delivery of siRNA...
November 8, 2016: Journal of Drug Targeting
Kevin Ita
With the increasing proportion of the global geriatric population, it becomes obvious that neurodegenerative diseases will become more widespread. From an epidemiological standpoint, it is necessary to develop new therapeutic agents for the management of Alzheimer's disease, Parkinson's disease, multiple sclerosis and other neurodegenerative disorders. An important approach in this regard involves the use of the transdermal route. With transdermal drug delivery systems (TDDS), it is possible to modulate the pharmacokinetic profiles of these medications and improve patient compliance...
November 8, 2016: Journal of Drug Targeting
Anup Jose, Suman Labala, Venkata Vamsi Krishna Venuganti
Skin cancer is one of the most widely prevalent cancer types with over expression of multiple oncogenic signaling molecules including STAT3. Curcumin is a natural compound with effective anti-cancer properties. The objective of this work was to investigate the liposomal co-delivery of curcumin and STAT3 siRNA by non-invasive topical iontophoretic application to treat skin cancer. Curcumin was encapsulated in cationic liposomes and then complexed with STAT3 siRNA. The liposomal nanocomplex was characterized for particle size, zeta-potential, drug release and stability...
November 7, 2016: Journal of Drug Targeting
Yanping Sun, Lei Xian, Haonan Xing, Jiankun Yu, Zhen Yang, Tianzhi Yang, Li Yang, Pingtian Ding
A nuclear localization signal (NLS) is a short amino acid sequence derived from eukaryotic nuclear proteins and viral proteins. Many NLS peptides can efficiently mediate the intranucleus transport of cargo molecules, so they have been widely used for non-viral gene transfer and shown potential ability to improve nuclear delivery of DNA. In order to maximally utilize NLS peptides to enhance gene transfer, several factors such as methods of incorporating NLS peptide, type and property of NLS peptide, number of NLS peptide, and spacer between NLS peptide and DNA should be considered...
December 2016: Journal of Drug Targeting
Mahima Mathur, V Kusum Devi
Emergence of hyperlipidemia in urban population of India and the world at large is very high and accounts to several fatal diseases. This condition is known to manifest elevated levels of lipids and/or lipoproteins. Serious limitations like inadequate solubility, less absorption, less bioavailability, ineffectiveness in lowering of cholesterol levels, patient incompliance and so on are noticed with majority of anti-hyperlipidemic drugs and dosage forms, which are used conventionally. To overcome these shortcomings, building technology platforms for development of appropriate dosage forms is the need of the hour...
December 2016: Journal of Drug Targeting
Anurag Verma, Juhi Dubey, Rahul Rama Hegde, Vaibhav Rastogi, J K Pandit
Helicobacter pylori have been subject to intense investigation since its discovery from gastric biopsy in 1982. This gastropathogen has been regarded as serious public health problem due to its association with dyspepsia, gastritis, gastroduodenal ulcers, mucus-associated lymphoid tissue lymphoma and gastric carcinoma. In vivo eradication of established H. pylori infections is difficult due to several factors such as gastric niche, coccoid form due to sub-minimum inhibitory concentration of antimicrobials, bacterial load, primary antibiotic resistance, patient compliance and stability of therapeutics in gastric acid secretion...
December 2016: Journal of Drug Targeting
Robert Hennig, Sabrina Kuespert, Alexandra Haunberger, Achim Goepferich, Rudolf Fuchshofer
The major risk factor for primary open-angle glaucoma is increased intraocular pressure stemming from elevated outflow resistance in the trabecular meshwork (TM) region. Integrins play a pivotal role in the TM by influencing its biological properties and growth factor signaling. Pathologic changes in the TM are partially mediated by growth factors like connective tissue growth factor (CTGF). Specific targeting of TM cells could play a critical clinical role by increasing the therapeutic efficacy of nanoparticles, e...
December 2016: Journal of Drug Targeting
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