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peptide drug delivery

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https://www.readbyqxmd.com/read/28213274/differentially-cleaving-peptides-as-a-strategy-for-controlled-drug-release-in-human-retinal-pigment-epithelial-cells
#1
Madhushree Bhattacharya, Sanjay Sarkhel, Jonne Peltoniemi, Robert Broadbridge, Marjo Tuomainen, Seppo Auriola, Arto Urtti
Currently, drug delivery to the posterior eye segment relies on intravitreal injections of therapeutics. This approach requires frequent injections and does not guarantee drug delivery to intracellular targets. Controlled release systems and nanoparticles are being investigated to mitigate these challenges but most of these approaches lack translational success to the clinics. In our present study, we report a peptide based delivery system that utilizes enzyme assisted cleavable linkers to release conjugated cargo within the retinal pigment epithelial (RPE) cells...
February 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28212490/vitamin-e-succinate-grafted-chitosan-oligosaccharide-rgd-conjugated-tpgs-mixed-micelles-loaded-with-paclitaxel-for-u87mg-tumor-therapy
#2
Yanzuo Chen, Shu Feng, Wenchao Liu, Zeting Yuan, Peihao Yin, Feng Gao
The poor therapeutic efficacy of hydrophobic chemotherapeutic drugs is an intrinsic limitation to successful chemotherapy. In the present study, a multi-task delivery system based on arginine-glycine-aspartic acid peptide (RGD) decorated vitamin E succinate (VES)-grafted-chitosan oligosaccharide (CSO)/RGD-conjugated D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS-RGD) mixed micelles (VeC/T-RGD MM) was first prepared for targeted delivery of paclitaxel (PTX), a hydrophobic anticancer drug, to improve the efficacy of U87MG tumor therapy...
February 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28206763/rational-design-of-a-polymer-with-robust-efficacy-for-intracellular-protein-and-peptide-delivery
#3
Hong Chang, Jia Lv, Xin Gao, Xing Wang, Hui Wang, Hui Chen, Xu He, Lei Li, Yiyun Cheng
The efficient delivery of biopharmaceutical drugs such as proteins and peptides into the cytosol of target cells poses substantial challenges owing to their large size and susceptibility to degradation. Current protein delivery vehicles have limitations such as the need for protein modification, insufficient delivery of large-size proteins or small peptides, and loss of protein function after the delivery. Here, we adopted a rational approach to design a polymer with robust efficacy for intracellular protein and peptide delivery...
February 16, 2017: Nano Letters
https://www.readbyqxmd.com/read/28202367/exosomes-therapy-delivery-tools-and-biomarkers-of-diseases
#4
REVIEW
Lucio Barile, Giuseppe Vassalli
Virtually all cells in the organism secrete extracellular vesicles (EVs), a heterogeneous population of lipid bilayer membrane-enclosed vesicles that transport and deliver payloads of proteins and nucleic acids to recipient cells, thus playing central roles in cell-cell communications. Exosomes, nanosized EVs of endosomal origin, regulate many pathophysiological processes including immune responses and inflammation, tumour growth, and infection. Healthy subjects and patients with different diseases release exosomes with different RNA and protein contents into the circulation, which can be measured as biomarkers...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28195491/prodrug-like-pegylated-protein-toxin-trichosanthin-for-reversal-of-chemoresistance
#5
Yingzhi Chen, Meng Zhang, Hongyue Jin, Yisi Tang, Aihua Wu, Qin Xu, Yongzhuo Huang
Multidrug resistance (MDR) is a main obstacle in cancer chemotherapy. The MDR mechanisms involve P-glycoprotein (P-gp) overexpression, abnormality of apoptosis-related protein, and altered expression of drug-targeting proteins. Therapeutic proteins are emerging as candidates for overcoming cancer MDR because of not only their large molecular size that potentially circumvents the P-gp-mediated drug efflux but also their distinctive bioactivity distinguished from small-molecular drugs. Herein we report trichosanthin, a plant protein toxin, possesses synergistic effect with paclitaxel (PTX) in the PTX-resistance A549/T nonsmall cell lung cancer (NSCLC) cells, by reversing PTX-caused caspase 9 phosphorylation and inducing caspase 3-dependent apoptosis...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28195032/ph-responsive-carriers-for-oral-drug-delivery-challenges-and-opportunities-of-current-platforms
#6
Lin Liu, WenDong Yao, YueFeng Rao, XiaoYang Lu, JianQing Gao
Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28194704/challenges-and-future-prospects-for-the-delivery-of-biologics-oral-mucosal-pulmonary-and-transdermal-routes
#7
Javier O Morales, Kristin R Fathe, Ashlee Brunaugh, Silvia Ferrati, Song Li, Miguel Montenegro-Nicolini, Zeynab Mousavikhamene, Jason T McConville, Mark R Prausnitz, Hugh D C Smyth
Biologic products are large molecules such as proteins, peptides, nucleic acids, etc., which have already produced many new drugs for clinical use in the last decades. Due to the inherent challenges faced by biologics after oral administration (e.g., acidic stomach pH, digestive enzymes, and limited permeation through the gastrointestinal tract), several alternative routes of administration have been investigated to enable sufficient drug absorption into systemic circulation. This review describes the buccal, sublingual, pulmonary, and transdermal routes of administration for biologics with relevant details of the respective barriers...
February 13, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28193211/display-of-single-chain-variable-fragments-on-bacteriophage-ms2-virus-like-particles
#8
Christopher A Lino, Jerri C Caldeira, David S Peabody
BACKGROUND: Virus-like particles (VLPs) of the RNA bacteriophage MS2 have many potential applications in biotechnology. MS2 VLPs provide a platform for peptide display and affinity selection (i.e. biopanning). They are also under investigation as vehicles for targeted drug delivery, using display of receptor-specific peptides or nucleic acid aptamers to direct their binding to specific cell-surface receptors. However, there are few molecules more suited to the precise targeting and binding of a cellular receptor than antibodies...
February 13, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28192660/in-vivo-imaging-of-the-stability-and-sustained-cargo-release-of-an-injectable-amphipathic-peptide-based-hydrogel
#9
Edith Oyen, Charlotte Martin, Vicky Caveliers, Annemieke Madder, Bruno Van Mele, Richard Hoogenboom, Sophie Hernot, Steven Ballet
Hydrogels are promising materials for biomedical applications such as tissue engineering and controlled drug release. In the last two decades, the subclass of peptide hydrogels is gaining increasing interest from the scientific community thanks to their numerous advantages, such as biocompatibility, biodegradability and most importantly, injectability. Here, we report on a hydrogel consisting of the amphipathic hexapeptide H-FEFQFK-NH2, which has previously shown promising in vivo properties in terms of releasing morphine...
February 13, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28192167/re-programming-pullulan-for-targeting-and-controlled-release-of-doxorubicin-to-the-hepatocellular-carcinoma-cells
#10
Anna Balasso, Stefano Salmaso, Patrizia Pontisso, Antonio Rosato, Santina Quarta, Alessio Malfanti, Francesca Mastrotto, Paolo Caliceti
A novel bioconjugate for hepatocellular carcinoma (HCC) targeting was obtained by pullulan re-programming, which involves the backbone oxidation and conjugation of targeting peptide and doxorubicin (Doxo) through a releasable linker. Preliminary in vivo studies showed that the oxidation of 40 glucopyranose units (GPU) out of 100 remarkably reduced the pullulan unspecific liver tropism. This oxidized polymer was functionalized with PreS1 to selectively target the HCC and with rhodamine (Rhod) as label to perform in vitro cell up-take investigations...
February 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28191948/supramolecular-trojan-horse-for-nuclear-delivery-of-dual-anticancer-drugs
#11
Yanbin Cai, Haosheng Shen, Jie Zhan, Mingliang Lin, Liuhan Dai, Chunhua Ren, Yang Shi, Jianfeng Liu, Jie Gao, Zhimou Yang
Nuclear delivery and accumulation is very important for many anticancer drugs which interact with DNA or its associated enzymes in nucleus. However, it is very difficult for neutrally and negatively charged anticancer drugs such as 10-hydroxycamptothecine (HCPT). Here we report a simple strategy to construct supramolecular nanomedicines for nuclear delivery of dual synergistic anticancer drugs. Our strategy utilizes the co-assembly of a negatively charged HCPT-peptide amphiphile and the positively charged cisplatin...
February 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28190655/development-of-helix-stabilized-cell-penetrating-peptides-containing-cationic-%C3%AE-%C3%AE-disubstituted-amino-acids-as-helical-promoters
#12
Hiroko Yamashita, Takashi Misawa, Makoto Oba, Masakazu Tanaka, Mikihiko Naito, Masaaki Kurihara, Yosuke Demizu
Cell-penetrating peptides (CPP) have attracted many scientists' attention as intracellular delivery tools due to their high cargo molecule transportation efficiency and low cytotoxicity. Therefore, in many research fields CPP, such as HIV-Tat and oligoarginine (Rn), are used to deliver hydrophilic drugs and biomolecules, including proteins, DNA, and RNA. We designed four types of CPP that contained cationic α,α-disubstituted amino acids (Api(C2Gu) and Api(C4Gu)) as helical promoters; i.e., 1-4 [FAM-β-Ala-(l-Arg-l-Arg-Xaa)3-(Gly)3-NH2 (1: Xaa=Api(C2Gu), 2: Xaa=Api(C4Gu)), 3: FAM-β-Ala-(l-Arg)8-Api(C2Gu)-(Gly)3-NH2, and 4: FAM-β-Ala-(l-Arg)5-Api(C2Gu)-(l-Arg)2-Api(C2Gu)-(Gly)3-NH2], and investigated their preferred secondary structures and cell membrane-penetrating ability...
February 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28188875/hydrophobic-ion-pairing-key-to-highly-payloaded-self-emulsifying-peptide-drug-delivery-systems
#13
Janine Griesser, Gergely Hetényi, Michael Moser, Frédéric Demarne, Vincent Jannin, Andreas Bernkop-Schnürch
AIM: The aim of this study was the formation and characterization of various ion pairs of therapeutic peptides with different surfactants in order to reach a high payload in self-emulsifying drug delivering systems (SEDDS). METHODS: Hydrophobic ion pairs (HIP) were formed between the anionic surfactants sodium docusate, dodecylsulfate and oleate and the peptides leuprorelin (LEU), insulin (INS) and desmopressin (DES). The efficiency of HIP formation was evaluated by quantifying the amount of formed complexes, log P value determination in n-octanol/water via HPLC and zeta potential measurements...
February 7, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28185449/positively-charged-combinatory-drug-delivery-systems-against-multi-drug-resistant-breast-cancer-beyond-the-drug-combination
#14
Xu Yan, Qingsong Yu, Linyi Guo, Wenxuan Guo, Shuli Guan, Hao Tang, Shanshan Lin, Zhihua Gan
The formation and development of cancer is usually accompanied by angiogenesis and is related to multiple pathways. The inhibition of one pathway by monotherapy might result in the occurrence of drug resistance, tumor relapse, or metastasis. Thus, a combinatory therapeutic system that targets several independent pathways simultaneously is preferred for the treatment. To this end, we prepared combinatory drug delivery systems consisting of cytotoxic drug SN38, pro-apoptotic KLAK peptide, and survivin siRNA with high drug loading capacity and reductive responsiveness for the treatment of multi-drug-resistant (MDR) cancer...
February 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28174779/improving-gelation-efficiency-and-cytocompatibility-of-visible-light-polymerized-thiol-norbornene-hydrogels-via-addition-of-soluble-tyrosine
#15
Han Shih, Hung-Yi Liu, Chien-Chi Lin
Hydrogels immobilized with biomimetic peptides have been used widely for tissue engineering and drug delivery applications. Photopolymerization has been among the most commonly used techniques to fabricate peptide-immobilized hydrogels as it offers rapid and robust peptide immobilization within a crosslinked hydrogel network. Both chain-growth and step-growth photopolymerizations can be used to immobilize peptides within covalently crosslinked hydrogels. A previously developed visible light mediated step-growth thiol-norbornene gelation scheme has demonstrated efficient crosslinking of hydrogels composed of an inert poly(ethylene glycol)-norbornene (PEGNB) macromer and a small molecular weight bis-thiol linker, such as dithiothreitol (DTT)...
February 8, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28170227/analyte-responsive-hydrogels-intelligent-materials-for-biosensing-and-drug-delivery
#16
Heidi R Culver, John R Clegg, Nicholas A Peppas
Nature has mastered the art of molecular recognition. For example, using synergistic non-covalent interactions, proteins can distinguish between molecules and bind a partner with incredible affinity and specificity. Scientists have developed, and continue to develop, techniques to investigate and better understand molecular recognition. As a consequence, analyte-responsive hydrogels that mimic these recognitive processes have emerged as a class of intelligent materials. These materials are unique not only in the type of analyte to which they respond but also in how molecular recognition is achieved and how the hydrogel responds to the analyte...
February 7, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28167424/construction-of-near-infrared-light-triggered-nanodumbbell-for-cancer-photodynamic-therapy
#17
Beibei Hou, Bin Zheng, Weitao Yang, Chunhong Dong, Hanjie Wang, Jin Chang
The application of photodynamic therapy (PDT) in deep tissue has been severely restricted by the poor photosensitizers loading and tissue-penetration of visible light for exciting the photosensitizers. How to prepare a nanocarrier with high drug loading amount and remote controllability still remains the challenge. In this article, a novel drug delivery system nanodumbbell was designed. The nanodumbbell was assembled from the hydrophobic upconverting nanoparticle (UCN) core and hydrophilic polymersome shell...
January 19, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28167286/recent-developments-in-anticancer-drug-delivery-using-cell-penetrating-and-tumor-targeting-peptides
#18
REVIEW
Shama Dissanayake, William A Denny, Swarna Gamage, Vijayalekshmi Sarojini
Efficient intracellular trafficking and targeted delivery to the site of action are essential to overcome the current drawbacks of cancer therapeutics. Cell Penetrating Peptides (CPPs) offer the possibility of efficient intracellular trafficking, and, therefore the development of drug delivery systems using CPPs as cargo carriers is an attractive strategy to address the current drawbacks of cancer therapeutics. Additionally, the possibility of incorporating Tumor Targeting Peptides (TTPs) into the delivery system provides the necessary drug targeting effect...
February 3, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28165817/pcm-and-tat-co-modified-liposome-with-improved-myocardium-delivery-in-vitro-and-in-vivo-evaluations
#19
Xin Wang, Hua Huang, Liangke Zhang, Yan Bai, Huali Chen
In this study, PCM and TAT co-modified liposome was developed as a novel drug carrier for myocardium delivery with evaluation of its in vitro and in vivo properties. Liposomes containing fluorescent probe coumarin-6 were prepared by thin-film hydration. The PCM ligands specifically bind to the PCM receptors in the extracellular connective tissue of primary myocardium cells (MCs), while the TAT ligands functioned as a classical cell penetrating peptide to make liposomes internalized by MCs. The unmodified liposome (L), PCM-modified liposome (PL), TAT-modified liposome (TL) and PCM and TAT co-modified liposome (PTL) were prepared and characterized...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28165730/kinetic-pathway-of-3-helix-micelle-formation
#20
JooChuan Ang, Benson T Jung, He Dong, Ting Xu
A subtle but highly pertinent factor in the self-assembly of hierarchical nanostructures is the kinetic landscape. Self-assembly of a hierarchical multicomponent system requires the intricate balance of noncovalent interactions on a similar energy scale that can result in several self-assembly processes occurring at different time scales. We seek to understand the hierarchical assemblies within an amphiphilic 3-helix peptide-PEG-lipid conjugate system in the formation process of highly stable 3-helix micelles (3HMs)...
February 15, 2017: Biomacromolecules
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