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Journal of Drug Targeting

Sofia Bisso, Anna Degrassi, Davide Brambilla, Jean-Christophe Leroux
Nanoparticulate systems can passively target regional lymphatic vessels and lymph nodes (LNs) after interstitial administration. Highly sensitive non-invasive imaging techniques, such as magnetic resonance imaging (MRI), can take advantage from particles' lymphotropic properties to provide a reliable tool to monitor lymphatic function and LN morphology with high spatial resolution. In this work, we developed and characterised a bioerodible nanosystem with MRI contrast properties, based on poly(ethylene glycol)-alendronate stabilised gadolinium calcium phosphate nanoparticles (NPs)...
December 4, 2018: Journal of Drug Targeting
Anjaneyulu Dirisala, Satoshi Uchida, Theofilus A Tockary, Naoto Yoshinaga, Junjie Li, Shigehito Osawa, Lahari Gorantla, Shigeto Fukushima, Kensuke Osada, Kazunori Kataoka
The major issues in messenger (m)RNA delivery are rapid mRNA degradation in the extracellular and intracellular spaces, which decreases the efficiency and duration for protein expression from mRNA. Stabilization of mRNA carriers using environment-responsive crosslinkings has promises to overcome these issues. Herein, we fine-tuned the structure of disulfide crosslinkings, which are selectively cleaved in the intracellular reductive environment, using the mRNA-loaded polyplex micelles (PMs) prepared from poly(ethylene glycol)-poly(L-lysine) (PEG-PLys) block copolymers, particularly by focusing on cationic charge density after the crosslinking...
November 30, 2018: Journal of Drug Targeting
Chengjie Lin, Zhigao Hu, Guandou Yuan, Huizhao Su, Yonglian Zeng, Zhenya Guo, Fudi Zhong, Keqing Jiang, He Songqing
Pancreatic cancer is one of the deadliest cancers across the world with an average 5-year survival rate of less than <6%. In this study, gemcitabine (GEM) and HIF1α-siRNA loaded GE-11 peptide conjugated liposome was successfully prepared and evaluated for its antitumor efficacy in pancreatic cancer cells. The GE11 increased the targeting specificity of liposome carrier and increased the intracellular concentrations in the cancer cells. Furthermore, synergistic combination of GEM and HIF1a-siRNA exhibited remarkable improvement in the declining of cancer cell proliferations...
November 27, 2018: Journal of Drug Targeting
Aditi Jhaveri, Ed Luther, Vladimir Torchilin
Glioblastomas (GBMs) are known to harbor subsets of cells known as tumor-initiating cells (TICs), which are responsible for the maintenance, invasiveness and recurrence of GBMs. Conventional chemotherapeutics act on rapidly dividing cells, sparing the TICs and result in tumor relapse. Resveratrol, (RES) has shown chemopreventive effects in all the major stages of cancer including initiation, promotion and progression, but poor physico-chemical and pharmacokinetic properties limit its use as a free drug. Hence we developed a liposomal formulation of RES (RES-L) to eradicate both the bulk tumor cells and TICs in GBMs...
November 26, 2018: Journal of Drug Targeting
Taher Nassar, Ayala Rohald, Natalya Naraykin, Dinorah Barasch, Orit Amsalem, Ponnandy Prabhu, Moshe Kotler, Simon Benita
Lopinavir (LPV), an efficient drug for HIV infection treatment, was incorporated into biodegradable PLGA nanocapsules (NCs) embedded in microparticles (MCPs) using the spray-drying technique in an attempt to bypass the P-gp efflux and protect the drug from CYP3A pre-systemic metabolism without ritonavir (RTV). SEM observations confirmed the formation of NCs and their entrapment in the MCPs. LPV-loaded NCs and free LPV were released from the MCPs at pH of 7.4 as evidenced by in vitro release studies. Results obtained from rat studies showed a 2-fold higher bioavailability of LPV following oral administration of the optimal formulation than Kaletra®, the marketed drug, showing that when properly entrapped, LPV can be effectively protected from CYP degradation in the gut as well as from the liver following systemic absorption...
November 23, 2018: Journal of Drug Targeting
Giovanna Lollo, Kevin Matha, Martina Bocchiardo, Jérôme Bejaud, Ilaria Marigo, Angelique Virgone-Carlotta, Thomas Dehoux, Charlotte Rivière, Jean Paul Rieu, Stephanie Briançon, Thomas Perrier, Olivier Meyer, Jean-Pierre Benoit
In this work, a novel lipophilic 5-FU derivative was synthetized and encapsulated into lipid nanocapsules (LNC). 5-FU was modified with lauric acid to give a lipophilic mono-lauroyl-derivative (5-FU-C12, MW of about 342 g/mol, yield of reaction 70%). 5-FU-C12 obtained was efficiently encapsulated into LNC (encapsulation efficiency above 90%) without altering the physico-chemical characteristics of LNC. The encapsulation of 5-FU-C12 led to an increased stability of the drug when in contact with plasma being the drug detectable until 3h following incubation...
November 21, 2018: Journal of Drug Targeting
Lijun Chen, Shifeng Li, Wande Li
Lysyl oxidase (LOX) and lysyl oxidase like proteins (LOXL), a family of extracellular matrix (ECM) crosslinking enzymes that have been recognized as playing an important role in fibrogenesis for more than 40 years, are logical targets for antifibrotic treatments. Pulmonary fibrosis, especially idiopathic pulmonary fibrosis (IPF), is a progressive and lethal disease characterized by excessive deposition of ECM in the lung parenchyma. In this review, we discuss the current clinical approaches for IPF and review members of LOX family-LOX, LOXL1, LOXL2, LOXL3 and LOXL4-in IPF patients and in animal models of bleomycin-induced pulmonary fibrosis...
November 20, 2018: Journal of Drug Targeting
Mary Caldorera-Moore, Julia E Vela Ramirez, Nicholas A Peppas
Whereas significant advancements have been made in our fundamental understanding of cancer, they have not yet translated into effective clinical cancer treatments. One of the areas that has the potential to improve the efficacy of cancer therapies is the development of novel drug delivery technologies. In particular, the design of pH-sensitive polymeric complexation hydrogels may allow for targeted oral delivery of a wide variety of chemotherapeutic drugs and proteins. In this work, poly(methacrylic acid grafted ethylene glycol) (P(MAA-g-EG) hydrogel nanoparticles were synthesized, characterized, and studied as matrix-type, diffusion-controlled, pH-responsive carriers to enable the oral delivery of the chemotherapeutic agent Interferon Alpha (IFN-α)...
November 20, 2018: Journal of Drug Targeting
Tinghua Hu, Shuo Yu, Yang Li, Hui Ren, Qian Ning, Jing Wang, Xuan Liang, Manxiang Li
Recurrence of lung adenocarcinoma has become one of the most frequent causes of major cancer incidence and mortality worldwide according to its frequently gained resistance to chemotherapies. In this study, we identified a poorly-studied kinase pyruvate dehydrogenase kinase isoform 2 (PDK2) as the most up-regulated kinase encoding gene in Cisplatin resistant lung adenocarcinoma. Additionally, PDK2-dependent Cisplatin-resistance promotes tumor growth of lung adenocarcinoma both in vitro and in vivo. Clinically, PDK2 expression was up-regulated in lung adenocarcinoma and was correlated to the poor prognosis of lung cancer patients...
November 20, 2018: Journal of Drug Targeting
Yuanhao Lv, Tingting Du, Ming Ji, Chunyang Wang, Songwen Lin, Nina Xue, Jing Jin, Heng Xu, Xiaoguang Chen
NSCLC is a worldwide challenge due to its high incidence and poor survival. PI3K-Akt-mTOR (PAM) pathway is one of the major pathways that mediate receptor tyrosine kinases (RTKs) signaling transduction. Aberration in PAM pathway are indicated correlating with poor prognosis of NSCLC. In this article, we highlighted a 2-amino-4-methylquinazoline derivative XH002 as PI3K/mTOR dual inhibitor with outstanding antitumor efficacy. Briefly, XH002 significantly repressed proliferation of PI3KCA mutant and/or P-S6RP, P-RAS40 high expressed NSCLC cells...
November 1, 2018: Journal of Drug Targeting
Guilherme Curty Lechuga, Mirian C S Pereira, Saulo C Bourguignon
Neglected tropical diseases caused by protozoan parasites affect the life of millions of people worldwide, causing mortality, morbidity and high economic and social burden. The search for new drug targets and therapeutic strategies to fight these pathogens are necessary, since many current drugs have limited effects, cause severe side effects and their use has resulted in pathogen resistance. Heme (iron protoporphyrin IX) is a ubiquitous molecule important in many biological processes, including the homeostasis, growth and development of human pathogens such as trypanosomatids (Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp...
October 31, 2018: Journal of Drug Targeting
Jian Zou, Zhang Zhang, Fang Xu, Shengyang Cui, Chunli Qi, Jinfeng Luo, Zhen Wang, Xiaoyun Lu, Zhengchao Tu, Xiaomei Ren, Liyan Song, Ke Ding
Collective data suggest tropomyosin-related kinase B (TrkB), which is correlated with the growth, migration and poor prognosis of neuroblastoma (NB), is a potential target for NB target therapy. Several Phase I/II pan-Trk inhibitors display impressive clinical outcomes but still no drug has been approved for general use. In this paper, we report a novel structural TrkB inhibitor GZD2202, a structural derivative of our previously identified DDR1 antagonists. GZD2202 demonstrates a moderate selectivity between Trk B/C and TrkA...
October 30, 2018: Journal of Drug Targeting
Josu Andrieu, Francesca Re, Laura Russo, Francesco Nicotra
Phage display is a powerful and widely used technique to find novel peptide ligands. A massive amount of peptide sequences have been identified for all kinds of materials, and peptides that may have targeting capabilities towards specific cells and tissues have received special attention in biomedical sciences. As a result, it is increasingly harder to follow all the work that has been done, which sometimes leads to many promising ligands receiving little attention, together with the publication of false positives that have already been found...
October 24, 2018: Journal of Drug Targeting
S Pascual-Gil, G Abizanda, E Iglesias, E Garbayo, F Prósper, M J Blanco-Prieto
Neuregulin-1 loaded poly(lactic-co-glycolic acid) (PLGA) microparticles hold great promise for treating acute myocardial infarction, as they have been proved to recover heart function and induce positive heart remodelling in preclinical studies. More recently, the inflammatory response of the heart after acute myocardial infarction (AMI) has been identified as one of the major mechanisms in cardiac tissue remodelling and repair. However, the connection between neuregulin-1 PLGA microparticles and inflammation is still not well characterised...
October 17, 2018: Journal of Drug Targeting
Selin Çeşmeli, Cigir Biray Avci
Cancer is one of the most common diseases all over the world; many people suffer from diverse types of cancer. However, currently there is no exact cure or therapy developed for cancer. On the other hand, nanoparticles are defined as microscopic particles that have dimensions less than 100 nm and they are known for their usage in health sciences and medicine, however a few harmful effects on different animal cells. Therefore, researchers began to use nanoparticles for cancer therapies and to develop new methods for much more effective therapies...
October 15, 2018: Journal of Drug Targeting
Kamel S Ahmed, Saied A Hussein, Abdelmoneim H Ali, Sameh A Korma, Qiu Lipeng, Chen Jinghua
In the last decades, pharmaceutical interested researches aimed to develop novel and innovative drug delivery techniques in the medical and pharmaceutical fields. Recently, phospholipid vesicles (Liposomes) are the most known versatile assemblies in the drug delivery systems. The discovery of liposomes arises from self-forming enclosed phospholipid bilayer upon coming in contact with the aqueous solution. Liposomes are uni or multilamellar vesicles consisting of phospholipids produced naturally or synthetically, which are readily non-toxic, biodegradable, and are readily produced on a large scale...
October 15, 2018: Journal of Drug Targeting
Shoshy Mizrahy, Anna Gutkin, Paolo Decuzzi, Dan Peer
One of the major challenges in drug development is the delivery of therapeutics to the central nervous system (CNS). The blood-brain barrier (BBB), which modulates the passage of molecules from the CNS, presents a formidable obstacle that limits brain uptake of therapeutics and, therefore, impedes the treatment of multiple neurological pathologies. Targeted nanocarriers present an excellent opportunity for drug delivery into the brain leveraging on endogenous receptors to transport therapeutics across the BBB endothelium...
October 8, 2018: Journal of Drug Targeting
Aishwarya Shivashankarappa, Konasur Rajesh Sanjay
The present research work describes the use of Photodynamic Therapy (PDT) ofdrug 5-aminolevulinic acid (5-ALA) conjugated with microbial synthesizedsilver nanoparticles on skin melanoma (B16F10) and epidermoid carcinoma (A431) cell lines. Silver nanoparticles were synthesized using the bacterial strain Bacillus licheniformis.The morphology of the nanoparticles were studied using Scanning Electron Microscopy (SEM) and elemental analysis of nanoparticles were carried out using Energy Dispersive X-Ray spectroscopy (EDX)...
October 3, 2018: Journal of Drug Targeting
Qing You, Talea Hopf, Werner Hintz, Stefan Rannabauer, Nadine Voigt, B van Wachem, Petra Henrich-Noack, Bernhard A Sabel
Because the blood-brain barrier (BBB) is an obstacle for drug-delivery, carrier systems such as polybutylcyanoacrylate (PBCA) nanoparticles (NPs) have been studied. Yet, little is known of how physiochemical features such as size, surfactants and surface charge influence BBB passage in vivo. We now used a rat model of in vivo imaging of the retina - which is brain tissue and can reflect the situation at the BBB - to study how size and surface charge determine NPs' ability to cross the blood-retina barrier (BRB)...
October 3, 2018: Journal of Drug Targeting
Amirhosein Kefayat, Fatemeh Ghahremani, Hasan Motaghi, Soodabeh Rostami, Masoud A Mehrgardi
In the present study, alive attenuated Salmonella typhi Ty21a was introduced as a vehicle for smart delivery of gold nanoparticles to the tumours' hypoxic regions. At the first step, the uptakes of gold nanoparticles with seven different decorations by S. typhi Ty21a was investigated using flow cytometry and inductively coupled plasma optical emission spectroscopy. The analyses demonstrated that folic acid functionalised gold nanoparticles (FA-GNPs) are the best candidates for producing the Golden Bacteria (GB)...
October 3, 2018: Journal of Drug Targeting
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