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Journal of Controlled Release: Official Journal of the Controlled Release Society

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https://www.readbyqxmd.com/read/28536049/peg-pcl-based-nanomedicines-a-biodegradable-drug-delivery-system-and-its-application
#1
REVIEW
Philip Grossen, Dominik Witzigmann, Sandro Sieber, Jörg Huwyler
The lack of efficient therapeutic options for many severe disorders including cancer spurs demand for improved drug delivery technologies. Nanoscale drug delivery systems based on poly(ethylene glycol)-poly(ε-caprolactone) copolymers (PEG-PCL) represent a strategy to implement therapies with enhanced drug accumulation at the site of action and decreased off-target effects. In this review, we discuss state-of-the-art nanomedicines based on PEG-PCL that have been investigated in a preclinical setting. We summarize the various synthesis routes and different preparation methods used for the production of PEG-PCL nanoparticles...
May 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28528740/angubindin-1-a-novel-paracellular-absorption-enhancer-acting-at-the-tricellular-tight-junction
#2
Susanne M Krug, Tomohiro Hayaishi, Daisuke Iguchi, Akihiro Watari, Azusa Takahashi, Michael Fromm, Masahiro Nagahama, Hiroyuki Takeda, Yoshiaki Okada, Tatsuya Sawasaki, Takefumi Doi, Kiyohito Yagi, Masuo Kondoh
A limiting barrier for mucosal absorption of drugs is the tight junction (TJ). TJs exist between two adjacent cells (bicellular TJ, bTJ) and at the sites where three cells meet (tricellular TJ, tTJ). We present a novel approach which employs a physiologically regulated pathway for the passage of large molecules through the tTJ. Main barrier-relevant tTJ proteins are tricellulin and angulin-1 to -3. We developed an angulin binder from Clostridium perfringens iota-toxin (Ib) whose receptor is angulin-1. An Ib fragment corresponding to amino acids 421-664 (Ib421-664) of iota-toxin proved to bind in cells expressing angulin-1 and -3, but not angulin-2...
May 18, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28527736/the-effects-of-non-invasive-radiofrequency-electric-field-hyperthermia-on-biotransport-and-biodistribution-of-fluorescent-60-fullerene-derivative-in-a-murine-orthotopic-model-of-breast-adenocarcinoma
#3
Norman A Lapin, Martyna Krzykawska-Serda, Sean Dilliard, Yuri Mackeyev, Maciej Serda, Lon J Wilson, Steven A Curley, Stuart J Corr
The aim of this study is to understand the combined and differential biokinetic effects of radiofrequency (RF) electric-field hyperthermia as an adjunctive therapy to [60]fullerene nanoparticle-based drug delivery systems in targeting the micro-vasculature and micro-environments of breast cancer tumors. Intravital microscopy (IVM) is an ideal tool to provide the spatial and temporal resolution needed for quantification in this investigation. The water-soluble and fluorescent [60]fullerene derivative (C60-serPF) was designed to be an amphiphilic nanostructure, which is able to cross several biological membranes and accumulate in tumor tissues by passing through abnormally leaky tumor blood vessels...
May 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28527735/advances-in-combination-therapy-of-lung-cancer-rationales-delivery-technologies-and-dosage-regimens
#4
REVIEW
Lan Wu, Donglei Leng, Dongmei Cun, Camilla Foged, Mingshi Yang
Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given to dosage regimens, i...
May 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28527734/singlet-oxygen-responsive-micelles-for-enhanced-photodynamic-therapy
#5
Xiaodan Li, Min Gao, Keting Xin, Ling Zhang, Dan Ding, Deling Kong, Zheng Wang, Yang Shi, Fabian Kiessling, Twan Lammers, Jianjun Cheng, Yanjun Zhao
Photodynamic therapy (PDT) efficacy is limited by the very short half-life and limited diffusion radius of singlet oxygen ((1)O2). We report a (1)O2-responsive micellar nanoplatform subject to considerable size-expansion upon light triggering to facilitate on-demand release of photosensitizers. Imidazole, a well-known (1)O2 scavenger, was incorporated in the hydrophobic core of amphiphilic copolymer micelles, and was used to coordinate with biocompatible Zn(2+) and encapsulate the photosensitizer chlorin e6 (Ce6)...
May 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28526437/a-fiber-distribution-model-for-predicting-drug-release-rates
#6
D G Petlin, A A Amarah, S I Tverdokhlebov, Y G Anissimov
Sustained drug release can be achieved by loading a drug into polymer material. The drug release can then be controlled for potential use in various biomedical applications. A model for drug release from a polymeric fibrous scaffold, which takes into account the distribution of fiber diameters within its structure, is developed here. It is demonstrated that the fiber diameter distribution significantly affects the drug release profile from electrospun scaffolds. The developed model indicates that altering the fiber distribution can be used as an additional tool to achieve an appropriate drug release profile...
May 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28522195/a-dpp-iv-resistant-glucagon-like-peptide-2-dimer-with-enhanced-activity-against-radiation-induced-intestinal-injury
#7
Jintao Gu, Shuo Liu, Nan Mu, Tonglie Huang, Wangqian Zhang, Huadong Zhao, Zhen Shu, Cun Zhang, Qiang Hao, Weina Li, Xiaochang Xue, Wei Zhang, Yingqi Zhang
Although radiotherapy is a highly effective treatment for abdominal or pelvic cancer patients, it can increase the incidence of severe gastrointestinal (GI) toxicity. As an intestinal growth factor, glucagon-like peptide 2 (GLP-2) has been shown to improve the preclinical models of both short bowel syndrome and inflammatory bowel disease by stimulating intestinal growth. Teduglutide ([Gly(2)]GLP-2), a recombinant human GLP-2 variant, has a prolonged half-life and stability as compared to the native GLP-2 peptide, but still requires daily application in the clinic...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28522194/aptamer-mediated-gene-therapy-enhanced-antitumor-activity-against-human-hepatocellular-carcinoma-in-vitro-and-in-vivo
#8
Shuangli Xiao, Zhongbing Liu, Ruolan Deng, Chunhong Li, Shaozhi Fu, Guilan Chen, Xiaoqin Zhang, Famin Ke, Siyun Ke, Xin Yu, Shurong Wang, Zhirong Zhong
A recombinant adenovirus carrying the tumor suppressor gene PTEN (Ad5-PTEN) is an effective antitumor agent against liver cancer. But the application of Ad5-PTEN has been greatly hindered by its auto-immunogenicity, non-specific toxicity to normal tissues, as well as poor stability in blood stream because of neutralizing antibody. Epithelial cell adhesion molecule (EpCAM) is over-expressed in most solid tumors and it has been identified to be a cancer stem cell surface marker in liver cancer. An RNA aptamer EpDT3 could specially bind with EpCAM and target EpCAM-positive cells...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28522193/ph-triggered-re-assembly-of-nanosphere-to-nanofiber-the-role-of-peptide-conformational-change-for-enhanced-cancer-therapy
#9
Peiqing Liang, Junjiong Zheng, Shulin Dai, Jiayu Wang, Zhaoqing Zhang, Ting Kang, Changyun Quan
pH-triggered conformational change and subsequent re-assembly of nanostructures provide a new strategy in nanomedicine for controlled drug release and enhanced therapy. Here, we reported the development of a novel pH-responsive nano-assembly as a drug carrier from peptide amphiphile (PA) consisting of mimicking peptide and stearic acid moieties. The mimicking peptide is a basic 17-amino acid peptide derived from antennapedia homeodomain, and undergoes a conformational transition of the secondary structure from β-sheet at pH7...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28522192/overcoming-photodynamic-resistance-and-tumor-targeting-dual-therapy-mediated-by-indocyanine-green-conjugated-gold-nanospheres
#10
Wei Li, Xiaomeng Guo, Fenfen Kong, Hanbo Zhang, Lihua Luo, Qingpo Li, Chunqi Zhu, Jie Yang, Yongzhong Du, Jian You
Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS)...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28522191/enhanced-tumor-therapy-via-drug-co-delivery-and-in-situ-vascular-promoting-strategy
#11
Mingxing Yin, Songwei Tan, Yuling Bao, Zhiping Zhang
Conventional tumor starving therapy by reducing its vessel density may be effective at early treatment but potentially contributes to tumor hypoxia, drug resistance and metastasis. A new strategy through enhancing tumor angiogenesis in combination with effective chemotherapeutic drugs, has shown successful tumor growth and spread inhibition. To achieve in situ release of angiogenic and antitumor drugs in tumor, we designed a precise ratiometric polymeric hybrid micelle system for co-delivering nitric oxide and paclitaxel...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28511928/rational-design-of-nanoparticles-towards-targeting-antigen-presenting-cells-and-improved-t-cell-priming
#12
Eva Zupančič, Caterina Curato, Maria Paisana, Catarina Rodrigues, Ziv Porat, Ana S Viana, Carlos A M Afonso, João Pinto, Rogério Gaspar, João N Moreira, Ronit Satchi-Fainaro, Steffen Jung, Helena F Florindo
Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules...
May 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28501705/doxorubicin-delivered-by-a-redox-responsive-dasatinib-containing-polymeric-prodrug-carrier-for-combination-therapy
#13
Jingjing Sun, Yanhua Liu, Yichao Chen, Wenchen Zhao, Qianyu Zhai, Sanjay Rathod, Yixian Huang, Suoqin Tang, Yong Tae Kwon, Christian Fernandez, Raman Venkataramanan, Song Li
Two novel prodrug polymers POEG-b-PSSDas (redox-sensitive) and POEG-b-PCCDas (redox-insensitive), which consist of poly(oligo(ethylene glycol) methacrylate) (POEG) hydrophilic blocks and dasatinib (DAS, an oncogenic tyrosine kinases inhibitor) conjugated hydrophobic blocks, were designed as dual-functional carriers for codelivery with doxorubicin (DOX). Both carriers retained antitumor activity of DAS and could form mixed micelles with DOX. Compared to POEG-b-PCCDas micelles, incorporation of disulfide linkage into POEG-b-PSSDas micelles facilitated efficient cleavage of DAS from prodrug micelles in tumor cells/tissues, leading to a higher level of anti-tumor activity in vitro and in vivo...
May 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28501673/chemotherapeutic-drug-photothermal-agent-co-self-assembling-nanoparticles-for-near-infrared-fluorescence-and-photoacoustic-dual-modal-imaging-guided-chemo-photothermal-synergistic-therapy
#14
Yang Li, Guihua Liu, Jinyuan Ma, Jinyan Lin, Huirong Lin, Guanghao Su, Dengyue Chen, Shefang Ye, Xiaoyuan Chen, Xuan Zhu, Zhenqing Hou
Multimodal imaging-guided synergistic combination therapy has shown great potential for cancer treatment. However, the nanocarrier-based theranostic systems suffer from batch-to-batch variation, complexity of multicomponent, poor drug loading, and carrier-related toxicity issues. To address these issues, herein we developed a novel carrier-free theranostic system with nanoscale characteristics for near-infrared fluorescence (NIRF) and photoacoustic (PA) dual-modal imaging-guided synergistic chemo-photothermal therapy (PTT)...
May 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28501672/combining-reactive-triblock-copolymers-with-functional-cross-linkers-a-versatile-pathway-to-disulfide-stabilized-polyplex-libraries-and-their-application-as-pdna-vaccines
#15
Philipp Heller, Dominika Hobernik, Ulrich Lächelt, Meike Schinnerer, Benjamin Weber, Manfred Schmidt, Ernst Wagner, Matthias Bros, Matthias Barz
Therapeutic nucleic acids such as pDNA hold great promise for the treatment of multiple diseases. These therapeutic interventions are, however, compromised by the lack of efficient and safe non-viral delivery systems, which guarantee stability during blood circulation together with high transfection efficiency. To provide these desired properties within one system, we propose the use of reactive triblock copolypept(o)ides, which include a stealth-like block for efficient shielding, a hydrophobic block based on reactive disulfides for cross-linking and a cationic block for complexation of pDNA...
May 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28501671/multifunctional-liposomes-delay-phenotype-progression-and-prevent-memory-impairment-in-a-presymptomatic-stage-mouse-model-of-alzheimer-disease
#16
Simona Mancini, Claudia Balducci, Edoardo Micotti, Daniele Tolomeo, Gianluigi Forloni, Massimo Masserini, Francesca Re
The failure of clinical trials largely focused on mild to moderate stages of Alzheimer disease has suggested to the scientific community that the effectiveness of Amyloid-β (Aβ)-centered treatments should be evaluated starting as early as possible, well before irreversible brain damage has occurred. Accordingly, also the preclinical development of new therapies should be carried out taking into account this suggestion. In the present investigation we evaluated the efficacy of a treatment with liposomes multifunctionalized for crossing the blood-brain barrier and targeting Aβ, carried out on young APP/PS1 Tg mice, taken as a model of pre-symptomatic disease stage...
May 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28501670/treg-recruiting-microspheres-prevent-inflammation-in-a-murine-model-of-dry-eye-disease
#17
Michelle L Ratay, Andrew J Glowacki, Stephen C Balmert, Abhinav P Acharya, Julia Polat, Lawrence P Andrews, Morgan V Fedorchak, Joel S Schuman, Dario A A Vignali, Steven R Little
Dry eye disease (DED) is a common ocular disorder affecting millions of individuals worldwide. The pathology of DED involves the infiltration of CD4(+) lymphocytes, leading to tear film instability and destructive inflammation. In the healthy steady state, a population of immunosuppressive T-cells called regulatory T-cells (Treg) regulates proliferation of immune cells that would otherwise lead to a disruption of immunological homeostasis. For this reason, it has been suggested that Tregs could restore the immunological imbalance in DED...
May 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28499816/tumor-ablation-using-low-intensity-ultrasound-and-sound-excitable-drug
#18
Ching-Hsuan Tung, Myung Shin Han, Young Kim, Jianjun Qi, Brian E O'Neill
The cell membrane is a semi-fluid container that defines the boundary of cells, and provides an enclosed environment for vital biological processes. A sound excitable drug (SED) that is non-cytotoxic to cells is developed to disrupt the plasma membrane under gentle ultrasound insonation, 1MHz, 1W/cm(2). The frequency and power density of insonation are within the physical therapy and medical imaging windows; thus the applied ultrasound is safe and not harmful to tissues. The insertion of SEDs into the plasma membrane is not toxic to cells; however, the intruding SEDs weaken the membrane's integrity...
May 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28495577/delivery-of-anti-inflammatory-peptides-from-hollow-pegylated-poly-nipam-nanoparticles-reduces-inflammation-in-an-ex-vivo-osteoarthritis-model
#19
James McMasters, Scott Poh, Jenny B Lin, Alyssa Panitch
Targeted delivery of anti-inflammatory osteoarthritis treatments have the potential to significantly decrease undesirable systemic side effects and reduce required therapeutic dosage. Here we present a targeted, non-invasive drug delivery system to decrease inflammation in an osteoarthritis model. Hollow thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) nanoparticles have been synthesized via degradation of a N,N'-bis(acryloyl)cystamine (BAC) cross-linked core out of a non-degradable pNIPAM shell. Sulfated 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) was copolymerized in the shell to increase passive loading of an anti-inflammatory mitogen-activated protein kinase-activated protein kinase 2 (MK2)-inhibiting cell-penetrating peptide (KAFAK)...
May 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28483514/therapeutic-targeting-strategies-using-endogenous-cells-and-proteins
#20
REVIEW
Neha N Parayath, Mansoor M Amiji
Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems...
May 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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