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Journal of Drug Targeting

Chao Chen, Binbin Wang
This study was conducted to evaluate the efficacy and possible mechanism of Brucea javanica oil emulsion (BJOE) on cachexia, by observing changes in related indexes in mice with cachexia and identifying the genes responsible based on gene chip analysis. In the BJOE treatment group, body weight loss, tumor growth and metastasis were found obviously inhibited, food and water intake had markedly increased, and survival time was significantly prolonged, as compared to the control group. Moreover, the BJOE witnessed improvement in body weight, prevention of tumor metastasis and overall increase in survival time, as compared to Indometacin (IND, the positive control medicine)...
July 13, 2017: Journal of Drug Targeting
Ravikumar Aalinkeel, Hilliard L Kutscher, Ajay Singh, Katherine Cwiklinski, Noor Khechen, Stanley A Schwartz, Paras N Prasad, Supriya D Mahajan
It is well established that overproduction and accumulation of the β-amyloid (Aβ) peptide 1-42 (Aβ(1-42)) is a trigger of the pathological cascade in Alzheimer's disease (AD) that manifests as cognitive impairment. Ginsenoside Rg3 is an important constituent of ginseng, plays an essential role in memory and improved cognition, and is known to produce antioxidant effects via the reduction of free radicals. Therefore, ginsenoside Rg3 may be a promising candidate as a neuroprotective agent for the treatment of AD...
July 12, 2017: Journal of Drug Targeting
Sungmun Lee, Leena Al-Kaabi, Aurélie Mawart, Ahsan Khandoker, Habiba Alsafar, Herbert F Jelinek, Kinda Khalaf, Ji-Ho Park, Yeu-Chun Kim
Highly echogenic and ultrasound-responsive microbubbles such as nitrogen, and perfluorocarbons have been exploited as ultrasound-mediated drug carriers. Here, we propose an innovative method for drug delivery using microbubbles generated from a chemical reaction. In a novel drug delivery system, luminol encapsulated in folate-conjugated bovine serum albumin nanoparticles (Fol-BSAN) can generate nitrogen gas (N2) by chemical reaction when it reacts with hydrogen peroxide (H2O2), one of reactive oxygen species (ROS)...
July 11, 2017: Journal of Drug Targeting
Vinay Sridhar, Sarika Wairkar, Ram Gaud, Amrita Bajaj, Pramod Meshram
Selegiline hydrochloride (SL), is an Anti-Parkinson's agent, has low oral bioavailability due to its high first pass metabolism and scarce oral absorption. In the present study, SL mucoadhesive nasal thermosensitive gel (SNT-gel) was prepared to enhance the bioavailability and subsequently, its concentration in the brain. The SNT-gel was prepared using Poloxamer 407-Chitosan combination and optimized formulation was further evaluated for physicochemical parameters. The comparative pharmacodynamic studies including behavioral studies, biochemical testing and histopathology of the brain was carried out in rats for SNT-gel, SL-nasal solution and SL Marketed Tablets...
July 6, 2017: Journal of Drug Targeting
Munazza Tamkeen Fatima, Ejaj Ahmad, Mehboob Hoque
Fibrin-based polymeric systems have now emerged as efficient carriers of drugs, growth factors, genes, and cells. Earlier, we have reported fibrin based plasma beads (PB), prepared from clotted whole plasma, as an efficient system for the controlled release of entrapped therapeutics. In the present study, we investigate the dual entrapment in erythrocytes and PB, as potential particulate antigen delivery system in rabbit and mice, with yeast invertase as the model antigen. Preparations used for immunization include- invertase entrapped in erythrocytes, the same further entrapped in PB, and crosslinked with glutaraldehyde...
July 3, 2017: Journal of Drug Targeting
Gaurav Sharma, Kanwaljit Chopra, Sanjeev Puri, Mahendra Bishnoi, Parveen Rishi, Indu P Kaur
Present work describes a novel composition for encapsulating TRPsiRNA (TRPV1 targeting siRNA) within lipid-matrix (4:1::glyceryl behnate:stearic acid) of SLNs, using suitably modified cold high-pressure homogenization technique. Optimization of the method and composition conducted using calf-thymus DNA (ctDNA), to avoid cost of TRPsiRNA molecules, resulted in small size (d50=50-100nm) and high entrapment (77.22-98.5%). Complete masking of extreme negative charge of both ctDNA (-34.50mV) and TRPsiRNA (-23.98mV) upon encapsulation in SLNs without employing cationic components is reported herein for the first time...
July 3, 2017: Journal of Drug Targeting
Carmen Garnacho, Silvia Muro
Enzyme replacement is a viable treatment for diseases caused by genetic deficiency of lysosomal enzymes. However, suboptimal access of enzymes to target sites limits this strategy. Polymer nanocarriers (NCs) coated with antibody against intercellular adhesion molecule 1 (ICAM-1), a protein overexpressed on most cells under disease states, enhanced biosdistribution and lysosomal delivery of these therapeutics. Whether this can be achieved using more biocompatible ICAM-1-targeting moieties is unknown, since intracellular uptake via this route is sensitive to the receptor epitope being targeted...
June 30, 2017: Journal of Drug Targeting
Arwa Kurabi, Daniel Schaerer, Lisa Chang, Kwang Pak, Allen F Ryan
Local treatment of middle ear (ME) disease currently requires surgical penetration of the tympanic membrane (TM). We previously discovered 12-mer peptides that are actively transported across the intact TM, a process that could be used for noninvasive drug delivery into the ME. To optimize transport and provide further understanding of the peptides transport mechanism, we extended two of the candidate peptides by six additional amino acids at random, and screened the resulting 18-mers libraries on TMs of rats with active bacterial otitis media (OM) for transport efficiency using phage display...
June 29, 2017: Journal of Drug Targeting
Dan Sun, Linshu Zhao, Junzhong Lin, Yun Zhao, Yu Zheng
The increase in multidrug resistance among colon cancer cells presents a challenge for the development of effective therapies. Small-molecule analogs of second mitochondria-derived activator of caspase (SMAC) mimetic in association with mixed lineage kinase domain-like protein (MLKL)-pDNA and z-VAD-fmk have shown ideal antitumor effects in colon cancer cells in vitro via induction of RIP3-dependent necroptosis. To achieve synergistic antitumor effects in vivo, liposomes loaded with SMAC mimetic, MLKL-pDNA and z-VAD-fmk have been developed using novel lipid fusion methods to co-localize the molecules of interest within the tumor cells...
June 26, 2017: Journal of Drug Targeting
Rajesh R Wakaskar
Nanoparticles govern an all-important role, in this day and age, in determining the tissue distribution of either hydrophobic or hydrophilic anti-cancer drugs by encapsulating them or by covalent attachment. The whole purpose is to systematically improve upon the existing anti-tumor efficacy of these drugs. Selective delivery of these chemotherapeutic agents to the compromised or diseased tissue is the key to avoid any potential toxicity problems. Certain types of nanoparticles, through various mechanisms such as active targeting or reversing multi-drug resistance, display immense potential in adding to the existing anti-tumor efficacy profile...
June 23, 2017: Journal of Drug Targeting
Shunping Han, Hongyue Zheng, Yanping Lu, Yue Sun, Anhao Huang, Weidong Fei, Xiaowei Shi, Xiuling Xu, Jingjing Li, Fanzhu Li
Glioma is the most common primary malignant brain tumor and the effect of chemotherapy is hampered by low permeability across the blood-brain-barrier (BBB). Borneol is a time-honored 'Guide' drug in traditional Chinese medicine and has been proved to be capable of promoting free drugs into the brain efficiently, but there are still risks that free drugs, especially anti-glioma drugs, may be disassembled and metabolized before penetrating the BBB and caused the whole brain distribution. The purpose of this paper was to investigate whether borneol intervention could facilitate the BBB penetration and assist glioma treatment by combining with doxorubicin (DOX) loaded PAMAM dendrimers drug delivery system modified with Angiopep-2 (a ligand of the low-density lipoprotein receptor-related protein, which overexpress both in the BBB and gliomas)...
June 21, 2017: Journal of Drug Targeting
Jingying Zhang, Diyin Shen, Min Jia, Haizhao Zhao, Yongmin Tang
To identify an agent with specific activity against B-lineage leukemia stem cells (B-LSCs), we generated norcantharidin (NCTD)-encapsulated liposomes modified with a novel humanized anti-human CD19 monoclonal antibody, Hm2E8b (Hm2E8b-NCTD-liposomes). These liposomes were specially designed to recognize and kill B-LSCs in vitro, and to decrease non-specific cytotoxicity to untargeted cells. Hm2E8b-NCTD-liposomes selectively ablated B-LSCs through targeting hepatic leukemia factor (HLF), which is implicated in hematopoietic stem cell regulation and is overexpressed in LSCs...
June 19, 2017: Journal of Drug Targeting
Hongzhi Qiao, Zhenzhu Zhu, Dong Fang, Yuan Sun, Chen Kang, Liuqing Di, Lei Zhang, Yahan Gao
Multidrug resistance (MDR) severely hinders the efficient chemotherapeutic treatments of cancer. d-α-Tocopherol polyethylene 1000 succinate (TPGS) based drug delivery system holds the potential of re-sensitizing resistant cancer cells. In this study, a TPGS prodrug containing both TPGS and mitoxantrone (MTO) via a disulphide bond was synthesised and assembled into micelle (TSMm) with a monodispersed diameter of 46.50 ± 1.12 nm. The disulphide bonds within the micelles could be cleaved in response to a high concentration of intracellular glutathione (GSH) after entering the tumour cells, leading a rapid release of MTO...
June 18, 2017: Journal of Drug Targeting
Siying Chen, Ti Meng, Xiaowei Zheng, Jiangxia Cai, Weipeng Zhang, Haisheng You, Jianfeng Xing, Yalin Dong
Multidrug resistance (MDR) is a serious obstacle in breast cancer patients which limits chemotherapeutic drugs application. Our previous study confirmed that overexpression of nucleophosmin (NPM) was closely related to MDR in methotrexate-resistant breast cancer cells (MCF-7/MTX), and NPM could be a potential therapeutic target for chemoresistance. In this work, we aim to investigate NPM-mediated resistance mechanism in breast carcinoma. The NPM level was strongly positive in breast carcinoma tissues compared with adjacent normal samples, which was associated with lymph node metastasis...
June 14, 2017: Journal of Drug Targeting
Argia Acarregui, Jesús Ciriza, Laura Saenz Del Burgo, Haritz Gurruchaga Iribar, José Yeste, Xavi Illa, Gorka Orive, Rosa M Hernández, Rosa Villa, Jose Luis Pedraz
Type I diabetes mellitus is characterised by the destruction of the insulin producing beta cells within the pancreas by the immune system. After the success of Edmonton protocol, islet transplantation has shown to be a promising therapy, but with the Achilles´ heel of the need of using immunosuppressive drugs. Currently, cell encapsulation technology represents a real alternative to protect transplanted islets from the host´s immune attack. Although preliminary in vitro studies with encapsulated cells have been traditionally performed under static conditions in terms of viability and efficiency, these static cultures do not represent a close approach to in vivo environments...
June 6, 2017: Journal of Drug Targeting
Nazlı Erdoğar, Güneş Esendağlı, Thorbjorn T Nielsen, Güldal Esendağlı-Yılmaz, Diğdem Yöyen-Ermiş, Batuhan Erdoğdu, Mustafa F Sargon, Hakan Eroğlu, Erem Bilensoy
Purpose The aim of this study is to test folate-conjugated cyclodextrin nanoparticles (FCD-1 and FCD-2) as a vehicle for reducing toxicity and increasing the antitumor efficacy of paclitaxel especially for metastatic breast cancer. Methods For the evaluation of PCX-loaded FCD nanoparticles, animal studies were realized in terms of survival rate, tumor size, weight change, metastazis and histopathological examination. Results FCD-1 displayed significant advantages such as efficient targeting of folate receptor positive breast cancer cells and having considerably lower toxicity compared to that of Cremophor®...
June 5, 2017: Journal of Drug Targeting
Abel Matondo, Sung Soo Kim
The role of the mitochondria, particularly its implications in cellular redox and oxidative balance is important for cell survival, and is involved in a variety of human diseases including Inflammatory Bowel Disease. In this review we address mitochondria physiology and reactive oxygen species as cognate to Inflammatory Bowel Disease. Several studies have reported altered mitochondria function in intestinal epithelium in Inflammatory Bowel Disease. However, mitochondrion significance in this disease has not been much investigated...
June 5, 2017: Journal of Drug Targeting
Xiaoyan Yang, Qian Zhao, Huali Yin, Xiaoyong Lei, Runliang Gan
MicroRNAs (miRNAs) are internal, non-coding, and ∼22 nt small RNAs that display cell- and tissue-specific expression. They play important regulatory roles in cell proliferation and chemo-sensitivity. This study focused on tumor-suppressive miR-33b-5p expression as well as its role in gastric cancer. MiR-33b-5p was found low expression in gastric cancer cell lines. Functionally, western blots and the luciferase reporter assay were used to confirm that HMGA2 was the potential target of miR-33b-5p. Next, we used CCK-8 kits to analyze the effect of miR-33b-5p combined chemotherapy drugs on cell inhibition rate, and flow cytometry to analyze cells apoptosis...
May 11, 2017: Journal of Drug Targeting
Mahima Mathur, V Kusum Devi
High prevalence of topical fungal infections is perceived in majority of nations worldwide accounting for numerous serious systemic complications. Of several fungal infections, candidiasis is one of the widespread infections which is manifested due to localisation and proliferation of fungi. Present pharmacotherapy offers an effective treatment but possesses serious limitations like inadequate solubility, ineffectiveness in lowering diseased condition and patient incompliance. Several attempts to overcome these shortcomings and building suitable technology platforms for development of appropriate dosage forms which can enhance effectiveness, patient acceptability while maintaining safety, efficacy and affordability of drug delivery, have been made...
September 2017: Journal of Drug Targeting
Hiraku Onishi, Ai Fukasawa, Andang Miatmoko, Kumi Kawano, Yuri Ikeuchi-Takahashi, Yoshiyuki Hattori
Macromolecule-antitumour drug conjugates can reach tumour sites specifically via the enhanced permeability and retention (EPR) effect. It is desirable to release the drug efficiently from the conjugate at acidic pH in the tumour tissue or in the endosomes of cancer cells. In this study, we attempted to produce a carrier system with a labile chemical bond at acidic pH. Adipic acid dihydrazide (ADH)-chondroitin sulfate (CS) (termed CS-ACH) was synthesised by a two-step method, with the introduction of formyl groups followed by reductive amination using ADH...
September 2017: Journal of Drug Targeting
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