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peptide drug delivery

Christoph Ernst, Julia Sindlinger, Dirk Schwarzer, Pierre Koch, Frank M Boeckler
The rigid conformation of constrained bicyclic peptides provides a number of advantages over larger protein-based ligands, including better chemical stability, enhanced tissue penetration, and a wider field of possible applications. Selective chemical modification strategies are able to extend the scope of applications not only in a therapeutic manner but also for the development of novel tools for protein capturing, bioimaging, and targeted drug delivery. Herein, we report the synthesis of an adamantane-based, symmetrical, tetravalent, sulfhydryl-specific peptide linker...
October 31, 2018: ACS Omega
Marta Jedynak, Remigiusz Worch, Małgorzata Podsiadła-Białoskórska, Jadwiga Chroboczek, Ewa Szołajska
Adenoviral dodecahedron is a virus-like particle composed of twelve penton base proteins, derived from the capsid of human adenovirus type 3. Due to the high cell penetration capacity, it was used as a vector for protein, peptide and drug delivery. Two receptors are known to be involved in the endocytic dodecahedron uptake, namely αv integrins and heparan sulfate proteoglycans. Since it has been observed, that dodecahedron efficiently penetrates a wide range of cancer cells, it suggests that other cellular compounds may play a role in the particle endocytosis...
November 2018: Biochimica et biophysica acta. Biomembranes
Fatemeh Araste, Khalil Abnous, Maryam Hashemi, Seyed Mohmmad Taghdisi, Mohammad Ramezani, Mona Alibolandi
Therapeutic peptides are attracting increasing attention for biomedical applications. Peptides present promising opportunities in targeted drug delivery due to their high specificity, selectivity, small dimensions, ease of modification, and high biocompatibility. During the last decade, the potential of peptides as therapeutics or targeting ligands has been boomed in nanotechnology and cancer research. This review summarizes various peptides as therapeutics and targeting ligands in cancer therapy. At first, two categories of tumor homing and cell penetrating peptides (CPPs) are introduced and then we will discuss the modification of CPPs...
November 5, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Dario Carradori, Andreia G Dos Santos, Julien Masquelier, Adrien Paquot, Patrick Saulnier, Joël Eyer, Véronique Préat, Giulio G Muccioli, Marie-Paule Mingeot-Leclercq, Anne des Rieux
The adsorption of a peptide (NFL-TBS.40-63 peptide (NFL)) known to induce neuronal stem cells (NSC) differentiation in vitro, at the surface of lipid nanocapsules (LNC) provides a targeting drug delivery system that penetrates subventricular zone-neural stem cells (SVZ-NSC) but not central canal-NSC (CC-NSC). We hypothesized preferential interactions could explaine, at least partially, the different properties of SVZ- and CC-NSC plasma membranes. The objective of this work was to compare SVZ- and CC-NSC plasma membrane lipid composition, fluidity and permeability...
November 5, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Chong Du, Yingqiu Qi, Yinlong Zhang, Yazhou Wang, Xiao Zhao, Huan Min, Xuexiang Han, Jiayan Lang, Hao Qin, Quanwei Shi, Zhengkui Zhang, Xiaodong Tian, Greg J Anderson, Ying Zhao, Guangjun Nie, Yinmo Yang
Pancreatic cancer (PCa) is one of the most lethal malignancies with 5-year survival rate of less than 8%. Current treatment regiments have a low response rate in unselected patients. However, the subgroup of PCa patients with BRCA mutations may benefit from poly-ADP-ribose polymerase inhibitors (PARPi) due to their biological properties in DNA repair. Dose-limiting toxicity in normal tissues is frequently observed when PARPi are combined with other chemotherapies, and the co-delivery of two drugs to tumor sites at an adequate concentration is challenging...
November 8, 2018: ACS Nano
Jing Zhang, Peng Zhang, Qian Zou, Xiang Li, Jianjiang Fu, Ying Luo, Xinli Liang, Yi Jin
Combination chemotherapy is a common clinical practice in cancer treatment. Here, cyclic RGD (arginylglycylaspartic acid) peptide was introduced to the surface of lipid/calcium/phosphate (LCP) asymmetric lipid layer nanoparticles for the co-delivery of paclitaxel (PTX) and gemcitabine monophosphate (GMP) (P/G-NPs). The sphere-like morphology of P/G-NPs displays a well-distributed particle size, and high entrapment efficiency and drug loading for both PTX and GMP, with a positive zeta potential. P/G-NPs were stable for up to 15 days...
November 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Wei Hong, Zehui Zhang, Lipeng Liu, Yining Zhao, Dexian Zhang, Mingchun Liu
Pneumococcal meningitis (PM), caused by Streptococcus pneumonia, remains a high-burden disease in developing countries. Antibiotic therapy has been limited due to the inefficiency of drug transport across the blood-brain barrier (BBB) and the emergence of drug-resistant strains. In our preliminary study, PEGylated nano-self-assemblies of bacitracin A (PEGylated Nano-BA12K ) demonstrated a strong antibacterial potency against S. pneumonia. In this study, the potential application of this micelle for the treatment of both Penicillin-sensitive and -resistant PM was studied...
November 2018: Drug Delivery
Xuejiao Li, Yahong Liu, Hongqi Tian
To overcome the side effects of and resistance to cisplatin, a variety of Pt(IV) prodrugs were designed and synthesized via different modifications including combination with lipid chains to increase hydrophobicity, conjugation with short peptide chains or nanoparticles to improve drug delivery, or addition of bioactive ligands to the axial positions of Pt(IV) complexes to exert dual-function effects. This review summarizes the recent progress in the development of Pt(IV) prodrugs conjugated with bioactive-targeting ligands, including histone deacetylase inhibitors, p53 agonists, alkylating agents, and nonsteroidal anti-inflammatory agents...
2018: Bioinorganic Chemistry and Applications
Andrew W Simonson, B S Atip Lawanprasert, Tyler D P Goralski, Kenneth C Keiler, Scott H Medina
We report the design, synthesis and efficacy of a new class of gel-like nano-carrier, or 'nanogel', prepared via templated electrostatic assembly of anionic hyaluronic acid (HA) polysaccharides with the cationic peptide amphiphile poly-L-lysine (PLL). Small molecules and proteins present during nanogel assembly become directly encapsulated within the carrier and are precisely released by tuning the nanogel HA:PLL ratio to control particle swelling. Remarkably, nanogels exhibit versatile and complimentary mechanisms of cargo delivery depending on the biologic context...
November 3, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Jose T A Oliveira, Pedro F N Souza, Ilka M Vasconcelos, Lucas P Dias, Thiago F Martins, Mauricio F Van Tilburg, Maria I F Guedes, Daniele O B Sousa
The efficiency of current antimicrobial drugs is noticeably decreasing and thus the development of new treatments is necessary. Natural and synthetic antimicrobial peptides (AMPs) have attracted great attention as promising candidates. Inspired on Mo-CBP3 , an antimicrobial protein from Moringa oleifera seeds, we designed and synthesized three AMPs named Mo-CBP3 -PepI, Mo-CBP3 -PepII, and Mo-CBP3 -PepIII. All these three peptides inhibited the growth of Candida species and pathogenic bacteria, penetrate into microbial cells, but none is hemolytic or toxic to human cells...
October 31, 2018: Biochimie
Norihisa Nakayama, Sho Takaoka, Megumi Ota, Kentaro Takagaki, Ken-Ichi Sano
We showed previously that a rigid and fibrous-structured cationic coiled-coil artificial protein had cell-penetrating activity that was significantly greater when compared with a less-structured cell-penetrating peptide. Nanomaterials with anisotropic structures often show aspect ratio-dependent unique physicochemical properties, as well as cell-penetrating activities. In this report, we have designed and demonstrated the cell-penetrating activity of a shorter cationic coiled-coil protein. An aspect ratio at 4...
November 1, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Jing Li, Shi Jin, Xue-Rong Dong, Xiao-Feng Han, Man-Yuan Wang
Hyaluronic acid (HA) and cell-penetrating peptide (CPP) R6H4-SA modified artesunate nanostructured lipid carrier (HA-R6H4-NLC/ART) for anti-tumor therapy was prepared. The physicochemical properties and in vitro drug release of HA-R6H4-NLC/ART were evaluated, and the uptake and cytotoxicity of liver cancer HepG2 cells were studied. The results showed that HA-R6H4-NLC/ART was spherical like in appearance, and the average particle size was about 160 nm. In vitro release experiments showed that the drug delivery system had sustained release characteristics...
September 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Yu Zhang, Hojjat Bazzazi, Raquel Lima E Silva, Niranjan B Pandey, Jordan J Green, Peter A Campochiaro, Aleksander S Popel
Purpose: Quantitative understanding of the transport of therapeutic macromolecules following intraocular injections is critical for the design of efficient strategies in treating eye diseases, such as neovascular (wet) age-related macular degeneration (AMD) and macular edema (ME). Antiangiogenic treatments, such as neutralizing antibodies against VEGF or recently characterized antiangiogenic peptides, have shown promise in slowing disease progression. Methods: We developed a comprehensive three-dimensional (3D) transport model for intraocular injections using published data on drug distribution in rabbit eyes following intravitreal and suprachoroidal (SC) injection of sodium fluorescein (SF), bevacizumab, and ranibizumab...
October 1, 2018: Investigative Ophthalmology & Visual Science
Aum Solanki, Rudy Smalling, Abraham H Parola, Ilana Nathan, Roni Kasher, Yashwant Pathak, Vijaykumar Sutariya
BACKGROUND: Humanin is a novel neuronal peptide that has displayed potential in the treatment of Alzheimer's Disease through the suppression of inflammatory IL-6 cytokine receptors. Such receptors are found throughout the body, including the eye, suggesting its other potential applications. Age-related macular degeneration (AMD) is the leading cause of blindness in the developing world. There is no cure for this disease, and currents treatments have several negative side effects associated with them, making finding other treatment options desirable...
October 31, 2018: Current Drug Delivery
Alexandros Marios Sofias, Trygve Andreassen, Sjoerd Hak
Ligand-decorated nanoparticles are extensively studied and applied for in vivo drug delivery and molecular imaging. Generally, two different ligand-decoration procedures are utilized; ligands are either conjugated with nanoparticle ingredients and incorporated during nanoparticle preparation, or they are attached to preformed nanoparticles by utilizing functionalized reactive surface groups (e.g. maleimide). Although the two procedures result in nanoparticles with very similar physicochemical properties, formulations obtained through the latter manufacturing process typically contain non-conjugated reactive surface groups...
October 30, 2018: Molecular Pharmaceutics
Gayong Shim, Dongyoon Kim, Sangbin Lee, Rae Sung Chang, Junho Byun, Yu-Kyoung Oh
We designed a bacterio-mimetic nanoparticle that can noncovalently control the orientation of attached antibodies. Liposomes with Fc-binding peptide (FcBP), formulated using FcBP-conjugated PEGylated lipid, were used as model nanoparticles. Compared with control nanoparticles surface-modified with antibody covalently attached via maleimide functional groups (Mal-NPs), FcBP-capped nanoparticles (FcBP-NPs) exhibited greater binding affinity to the target protein. Human epidermal growth factor receptor 2 (HER2)-specific antibody-modified FcBP-NPs (HER2/FcBP-NPs) showed 5...
October 24, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Annika Klimpel, Ines Neundorf
The mitochondrial organelle is associated with many diseases, including diabetes, age-related neuro-degenerative diseases and cancer. Therefore, the effective delivery of drug molecules to mitochondria became increasingly important during the past years. Within this work, we designed and analyzed bifunctional hybrid peptides comprised of a mitochondrial targeting sequence (MTS) attached to a cell-penetrating peptide (CPP). Our results demonstrate that choice of the MTS must be carefully undertaken, since not every MTS that was selected was comparably capable to target mitochondria...
October 24, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Shinichi Kokubu, Kelly A Eddinger, Thi M-D Nguyen, Lena Libertad Huerta-Esquivel, Shigeki Yamaguchi, Peter W Schiller, Tony L Yaksh
Background and aims We systematically characterized the potency and side effect profile of a series of small opioid peptides with high affinity for the mu opioid receptor. Methods Male Sprague Dawley rats were prepared with intrathecal (IT) catheters, assessed with hind paw thermal escape and evaluated for side effects including Straub tail, truncal rigidity, and pinnae and corneal reflexes. In these studies, DMT-DALDA (dDAL) (H-Dmt-D-Arg-Phe-Lys-NH2 MW=981), dDALc (H-Dmt-Cit-Phe-Lys-NH2 MW=868), dDALcn (H-Dmt-D-Cit-Phe-Nle-NH2 MW=739), TAPP (H-Tyr-D-Ala-Phe-Phe-NH2 MW=659), dDAL-TICP ([Dmt1]DALDA-(CH2)2-NH-TICP[psi]; MW=1519), and dDAL-TIPP (H-Dmt-D-Arg-Phe-Lys(Nε-TIPP)-NH2 were examined...
October 25, 2018: Scandinavian Journal of Pain
Michel L Leite, Kamila B Sampaio, Fabrício F Costa, Octávio L Franco, Simoni C Dias, Nicolau B Cunha
The constant demand for new antibiotic drugs has driven efforts by the scientific community to prospect for peptides with a broad spectrum of action. In this context, antimicrobial peptides (AMPs) have acquired great scientific importance in recent years due to their ability to possess antimicrobial and immunomodulatory activity. In the last two decades, plants have attracted the interest of the scientific community and industry as regards their potential as biofactories of heterologous proteins. One of the most promising approaches is the use of viral vectors to maximize the transient expression of drugs in the leaves of the plant Nicotiana benthamiana...
October 18, 2018: Anais da Academia Brasileira de Ciências
Kotaro Matsumoto, Tan Le Hoang Doan, Ngoc Xuan Dat Mai, Keigo Nakai, Aoi Komatsu, Fuyuhiko Tamanoi
Biodegradable PMO (Periodic Mesoporous Organosilica) has emerged as a promising type of mesoporous silica based nanoparticles for clinical translation. We as well as others have synthesized and characterized three types of nanoparticles containing disulfide, tetrasulfide or peptide-like bonds within their framework. Biodegradable PMO has high drug loading efficiency and can be taken up into cancer cells. Our experiments utilizing the chicken egg tumor model uncovered excellent capability to accumulate and deliver anticancer drugs to the tumor...
2018: Enzymes
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