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https://www.readbyqxmd.com/read/30009885/battle-of-glp-1-delivery-technologies
#1
REVIEW
Minzhi Yu, Mason M Benjamin, Santhanakrishnan Srinivasan, Emily E Morin, Ekaterina I Shishatskaya, Steven P Schwendeman, Anna Schwendeman
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) belong to an important therapeutic class for treatment of type 2 diabetes. Six GLP-1 RAs, each utilizing a unique drug delivery strategy, are now approved by the Food and Drug Administration (FDA) and additional, novel GLP-1 RAs are still under development, making for a crowded marketplace and fierce competition among the manufacturers of these products. As rapid elimination is a major challenge for clinical application of GLP-1 RAs, various half-life extension strategies have been successfully employed including sequential modification, attachment of fatty-acid to peptide, fusion with human serum albumin, fusion with the fragment crystallizable (Fc) region of a monoclonal antibody, sustained drug delivery systems, and PEGylation...
July 12, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/30008428/initial-risk-assessment-as-part-of-the-quality-by-design-in-peptide-drug-containing-formulation-development
#2
E Pallagi, R Ismail, T L Paál, I Csóka
Risk Assessment (RA) is the key element of the Quality by Design (QbD) approach recommended by the pharmaceutical regulatory bodies. This research paper aimed to implement the regulatory requirements, the QbD thinking and the RA from the first steps of the oral peptide formulation development. The authors intended to give a general recommendation about the application possibilities of this methodology, to demonstrate the risk factors and the required decision points. Later, this paper presents a concrete development in practice...
July 3, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/30006163/thiodipeptides-targeting-the-intestinal-oligopeptide-transporter-as-a-general-approach-to-improving-oral-drug-delivery
#3
David W Foley, Ravindra B Pathak, Theresa R Phillips, Gayle L Wilson, Patrick D Bailey, Myrtani Pieri, Anish Senan, David Meredith
The broad substrate capacity of the intestinal oligopeptide transporter, PepT1, has made it a key target of research into drug delivery. Whilst the substrate capacity of this transporter is broad, studies have largely been limited to small peptides and peptide-like drugs. Here, we demonstrate for the first time that a diverse range of drugs can be targeted towards transport by PepT1 using a hydrolysis resistant carrier. Eleven prodrugs were synthesized by conjugating modified dipeptides containing a thioamide bond to the approved drugs ibuprofen, gabapentin, propofol, aspirin, acyclovir, nabumetone, atenolol, zanamivir, baclofen and mycophenolate...
June 30, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30003954/surface-functionalized-dendrimers-as-controlled-release-delivery-nanosystems-for-tumor-targeting
#4
REVIEW
Maryam Ghaffari, Gholamreza Dehghan, Fereydoon Abedi-Gaballu, Soheila Kashanian, Behzad Baradaran, Jafar Ezzati Nazhad Dolatabadi, Dusan Losic
Dendrimers are nano-sized and three-dimensional macromolecules with well-defined globular architecture and are widely used in various aspects such as drug and gene delivery owing to multivalent and host-guest entrapment properties. However, dendrimers like other nanomaterials have some disadvantages for example rapid clearance by reticuloendothelial system, toxicity due to interaction of amine terminated group with cell membrane, low transfection efficiency and lack of controlled release behavior, which reduce their therapeutic efficiency...
July 9, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/30003620/tracking-the-fate-of-porous-silicon-nanoparticles-delivering-a-peptide-payload-by-intrinsic-photoluminescence-lifetime
#5
Yusung Jin, Dokyoung Kim, Hajung Roh, Sojeong Kim, Sazid Hussain, Jinyoung Kang, Chan-Gi Pack, Jun Ki Kim, Seung-Jae Myung, Erkki Ruoslahti, Michael J Sailor, Song Cheol Kim, Jinmyoung Joo
A nanoparticle system for systemic delivery of therapeutics is described, which incorporates a means of tracking the fate of the nanocarrier and its residual drug payload in vivo by photoluminescence (PL). Porous silicon nanoparticles (PSiNPs) containing the proapoptotic antimicrobial peptide payload, D [KLAKLAK]2 , are monitored by measurement of the intrinsic PL intensity and the PL lifetime of the nanoparticles. The PL lifetime of the PSiNPs is on the order of microseconds, substantially longer than the nanosecond lifetimes typically exhibited by conventional fluorescent tags or by autofluorescence from cells and tissues; thus, emission from the nanoparticles is readily discerned in the time-resolved PL spectrum...
July 13, 2018: Advanced Materials
https://www.readbyqxmd.com/read/30001801/the-antitumor-effect-of-tat-dcf1-peptide-in-glioma-cells
#6
Jiao Wang, Qian Wang, Fangfang Zhou, Jie Li, Qian Li, Hong Zhou, Shiman Li, Sujuan Ma, Tieqiao Wen
BACKGROUND: Glioblastoma is one of the most malignant brain cancer, thus, establishing an effective therapy is paramount. Our previous results indicate that dendritic cell-derived factor (DCF1) is an attractive candidate for therapy against Glioblastoma, since its overexpression in Glioblastoma U251 cells leads to apoptosis. However, the delivery approach limits its clinical application, in this paper, we expressed TAT-DCF1 fusion protein in E.coli in order to surmount its current delivery problems...
June 25, 2018: Neuropeptides
https://www.readbyqxmd.com/read/30001104/assembly-pathway-selection-of-designer-sap-and-fabrication-of-hierarchical-scaffolds-for-neural-regeneration
#7
Yuyuan Zhao, Rong Zhu, Xiyong Song, Zheng Ma, Shengfeng Chen, Dongni Wu, Fufeng Liu, Songying Ouyang, Jianguo Zhang, Seeram Ramakrishna, Xiaofeng Zhu, Liumin He
RADA 16-I self-assembling peptide (SAP) has been modified with various functional motifs to improve its performances in biomedical applications. Nevertheless, the assembly mechanisms of designer functional RADA 16-I SAPs (F-SAPs) have not been clearly illustrated. The main problem is the difficult in preparing completely molecular aqueous solution of F-SAP. We demonstrated that different procedures for preparing F-SAP solution could result in the formation of different conformations and consequently micro/macroscopic morphologies...
July 12, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29997043/functionalized-carbon-nanotubes-as-emerging-delivery-system-for-the-treatment-of-cancer
#8
REVIEW
Shubhangi Mahajan, Abhimanyu Patharkar, Kaushik Kuche, Rahul Maheshwari, Pran Kishore Deb, Kiran Kalia, Rakesh K Tekade
In recent time, carbon nanotubes (CNTs) have gained vital importance for pharmaceutical formulation scientist for delivering drugs and genes, owing to their excellent surface properties. For example, their aspect ratio is thought to be responsible for their excellent cell penetration aptitude; anisotropic conductivity/semi-conductivity along their axis is ideal for integration with nervous and muscular tissue; an ultrahigh surface area maximizes their ability to "talk" with biological matter; the hollow interior provides an enormous cargo-carrying capacity for drug delivery; and their exteriors are readily functionalized to permit tailoring of solubility and biological recognition...
July 8, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29992622/development-of-an-orthotopic-canine-prostate-cancer-model-expressing-human-grpr
#9
Michael F Tweedle, Haiming Ding, William T Drost, Joshua Dowell, James Spain, Mathew Joseph, Said M Elshafae, Maria-Isabela Menendez, Li Gong, Shankaran Kothandaraman, Wessel P Dirksen, Chadwick L Wright, Robert Bahnson, Michael V Knopp, Thomas J Rosol
BACKGROUND: Ace-1 canine prostate cancer cells grow orthotopically in cyclosporine immunosuppressed laboratory beagles. We previously transfected (human Gastrin-Releasing Peptide Receptor, huGRPr) into Ace-1 cells and demonstrated receptor-targeted NIRF imaging with IR800-G-Abz4-t-BBN, an agonist to huGRPr. Herein, we used the new cell line to develop the first canine prostate cancer model expressing a human growth factor receptor. METHODS: Dogs were immunosuppressed with cyclosporine, azathioprine, prednisolone, and methylprednisolone...
July 11, 2018: Prostate
https://www.readbyqxmd.com/read/29990379/cd177-mediated-nanoparticle-targeting-of-human-and-mouse-neutrophils
#10
Heini M Miettinen, Jeannie M Gripentrog, Connie I Lord, Jon O Nagy
Neutrophils are the most abundant white blood cells, with a vital role in innate immune defense against bacterial and fungal pathogens. Although mostly associated with pathological processes directly related to immune defense, they can also play a detrimental role in inflammatory conditions and have been found to have a pro-metastatic role in the spread of cancer cells. Here, we explore ways to temporarily suppress these detrimental activities. We first examined the possibility of using siRNA and antisense oligonucleotides (ASOs) for transient knockdown of the human and mouse C5a receptor, an important chemoattractant receptor involved in neutrophil-mediated injury that is associated with myocardial infarction, sepsis, and neurodegenerative diseases...
2018: PloS One
https://www.readbyqxmd.com/read/29987301/a-novel-%C3%AE-enolase-targeted-drug-delivery-system-for-high-efficacy-prostate-cancer-therapy
#11
Luyao Wang, Mengke Qu, Shiqi Huang, Yu Fu, Liuqing Yang, Shanshan He, Lin Li, Zhirong Zhang, Qing Lin, Ling Zhang
Prostate cancer, one of the leading causes of disease and death in men all over the world, is challenging to treat. α-Enolase, a multifunctional protein, is overexpressed on human prostate carcinoma cells, and thereby it is a potential target for treatment of prostate cancer. In the current study, the pHCT74 peptide was used to construct a kind of highly targeted liposome (pHCT74-lipo) loaded with doxorubicin (pHCT74-lipo-Dox), which specifically targeted α-enolase on prostate tumour cells. Compared with liposomes without pHCT74 modification, pHCT74-lipo-Dox displayed a superior intracellular internalization with enhanced tumour cytotoxicity...
July 10, 2018: Nanoscale
https://www.readbyqxmd.com/read/29986554/-synthesis-of-cell-penetrating-peptide-decorated-magnetic-nanoparticles-loading-cisplatin-for-nasopharyngeal-cancer-therapy
#12
L M Quan, Y Zhong, H H Weng
Objective: To synthesize cisplatin loaded and cell penetrating peptide TAT decorated magnetic nanoparticles and to observe the inhibiting effect in vitro on nasopharyngeal cancer therapy. Method: The aldehyde sodium alginate coated magnetic nanoparticles (ASA-MNPs) was prepared as the drug delivery system, which was covalently attached by PEGylation TAT (TAT-ASA-MNPs) via condensation of aldehyde with amino group and then coordinated with cisplatin (TAT-ASA-MNPs@CDDP). The complex was characterized by H-NMR and FT-IR...
July 2018: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/29986452/design-synthesis-and-characterization-of-novel-co-polymers-decorated-with-peptides-for-the-selective-nanoparticle-transport-across-the-cerebral-endothelium
#13
Andrea P Falanga, Pietro Melone, Roberta Cagliani, Nicola Borbone, Stefano D'Errico, Gennaro Piccialli, Paolo A Netti, Daniela Guarnieri
The development of new strategies for enhancing drug delivery to the brain represents a major challenge in treating cerebral diseases. In this paper, we report on the synthesis and structural characterization of a biocompatible nanoparticle (NP) made up of poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG) co-polymer (namely PELGA) functionalized with the membranotropic peptide gH625 (gH) and the iron-mimicking peptide CRTIGPSVC (CRT) for transport across the blood-brain barrier (BBB). gH possesses a high translocation potency of the cell membrane...
July 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29982104/nrp-1-targeted-and-cargo-loaded-exosomes-facilitate-simultaneous-imaging-and-therapy-of-glioma-in-vitro-and-in-vivo
#14
Gang Jia, Yong Han, Yanli An, Yinan Ding, Chen He, Xihui Wang, Qiusha Tang
Currently, glioma treatment is limited by two main factors: timely detection at onset or relapse and restriction of drugs by the blood-brain barrier (BBB) from entering the brain and influencing tumor growth. However, a safe BBB-traversing drug delivery system has brought new hope to glioma treatment. Exosomes have strong cargo-loading capacity and have the ability to cross the BBB. They can also be conferred with the ability for targeted delivery. Therefore, exosomes have great promise to be a targeted drug delivery vehicles...
June 21, 2018: Biomaterials
https://www.readbyqxmd.com/read/29981357/injectable-and-protease-degradable-hydrogel-for-sirna-sequestration-and-triggered-delivery-to-the-heart
#15
Leo L Wang, Jennifer J Chung, Elizabeth C Li, Selen Uman, Pavan Atluri, Jason A Burdick
Injectable hydrogels have significant therapeutic potential for treatment of myocardial infarction (MI) through tissue bulking and local drug delivery, particularly for small interfering RNAs (siRNAs). As siRNA targets are identified as potential treatments for MI, hydrogels may bolster efficacy through local and sustained release. Here, we designed an injectable hydrogel to respond to local upregulation in proteolytic activity after MI to erode and release siRNA against MMP2 (siMMP2), a target implicated in deleterious remodeling...
July 4, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29981355/sedds-a-game-changing-approach-for-the-oral-administration-of-hydrophilic-macromolecular-drugs
#16
REVIEW
Arshad Mahmood, Andreas Bernkop-Schnürch
Since the development of self-emulsifying drug delivery systems (SEDDS) in 1980's, they attract the attention of researchers in order to confront the challenge of poor water-solubility of orally given drugs. Within recent years, SEDDS were also discovered for oral administration of hydrophilic macromolecular drugs such as peptides, proteins, polysaccharides and pDNA. Due to hydrophobic ion pairing (HIP) with oppositely charged lipophilic auxiliary agents the resulting complexes can be incorporated in the lipophilic phase of SEDDS...
July 4, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29979588/conjugation-of-amphiphilic-proteins-to-hydrophobic-ligands-in-organic-solvent
#17
Antonietta Maria Lillo, Ciana Lopez, Trideep Rajale, Hung-Ju Yen, Harsha Magurudeniya, M Lisa Phipps, Eva Rose Murdock Balog, Timothy C Sanchez, Srinivas Iyer, Hsing-Lin Wang, Ryszard Michalczyk, Reginaldo C Rocha, Jennifer S Martinez
Protein-ligand conjugations are usually carried out in aqueous media in order to mimic the environment within which the conjugates will be used. In this work, we focus on the conjugation of amphiphilic variants of elastin-like polypeptide (ELP), short elastin (sEL), to poorly water-soluble compounds like OPPVs (p-phenylene vinylene oligomers), triarylamines, and polypyridine-metal complexes. These conjugations are problematic when carried out in aqueous phase because hydrophobic ligands tend to avoid exposure to water, which in turn causes the ligand to self-aggregate and/or interact non-covalently with hydrophobic regions of the amphiphile...
July 6, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29979572/murine-and-non-human-primate-dendritic-cell-targeting-nanoparticles-for-in-vivo-generation-of-regulatory-t-cells
#18
Sebastian O Stead, Svjetlana Kireta, Steven James Peter McInnes, Francis D Kette, Kisha N Sivanathan, Juewan Kim, Eduardo J Cueto-Diaz, Frederique Cunin, Jean-Olivier Durand, Christopher J Drogemuller, Robert P Carroll, Nicolas H Voelcker, Patrick T Coates
Porous silicon nanoparticles (pSiNP), modified to target dendritic cells (DC), provide a novel strategy for the delivery of immunosuppressive drugs. Here, we aimed to develop a DC-targeting pSiNP displaying c-type lectin; Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) and CD11c monoclonal antibodies. The in vivo tracking of these fluorescent DC-targeting nanoparticles was assessed in both C57BL/6 mice and common marmosets (Callithrix jacchus) by i.v. injection (20 mg/kg)...
July 6, 2018: ACS Nano
https://www.readbyqxmd.com/read/29979563/targeting-delivery-of-lidocaine-and-cisplatin-by-nanogel-enhances-chemotherapy-and-alleviates-metastasis
#19
Xiurong Gao, Hui Yang, Min Wu, Kun Shi, Cheng Zhou, Qian Yang, JinRong Peng
Tumor growth inhibition and adverse effect reduction together with metastasis alleviation are still the challenges need to be overwhelmed in cancer chemotherapy. Combinational therapy provides an alternative solution for these challenges. And nanoparticles are the ideal carriers for combinational therapy due to their versatile drugs loading capacity and versatile tumor-targeting strategies. In this study, a cRGDfk modified nanogel system has utilized to co-load lidocaine, a voltage-gated Na+ channels inhibitor, and cisplatin, a common anticancer drug to obtain a tumor-targeted dual drugs-loaded nanogel system...
July 6, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29977402/design-and-biological-characterization-of-novel-cell-penetrating-peptides-preferentially-targeting-cell-nuclei-and-subnuclear-regions
#20
Anja Gronewold, Mareike Horn, Ines Neundorf
Within this study, we report about the design and biological characterization of novel cell-penetrating peptides (CPPs) with selective suborganelle-targeting properties. The nuclear localization sequence N50, as well as the nucleoli-targeting sequence NrTP, respectively, were fused to a shortened version of the cell-penetrating peptide sC18. We examined cellular uptake, subcellular fate and cytotoxicity of these novel peptides, N50-sC18* and NrTP-sC18*, and found that they are nontoxic up to a concentration of 50 or 100 µM depending on the cell lines used...
2018: Beilstein Journal of Organic Chemistry
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