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peptide drug delivery

Wei-Hsien Hsieh, Jiahorng Liaw
Self-assembled cyclic peptide nanotubes (cPNTs) have recently drawn particular attention as one of the most intriguing nanostructures in the field of nanotechnology. Given their unique features including high surface area, increased drug loading, environmental stability, enhanced permeation, and modifiable drug release, these hollow tubular structures can be constructed with cyclic di-, tri-, tetra-, hexa-, octa-, and decapeptides with various amino acid sequences, enantiomers, and functionalized side chains and can be applied for antiviral and antibacterial drugs, drug delivery and gene delivery vectors, organic electronic devices, and ionic or molecular channels...
January 2019: Journal of Food and Drug Analysis
Antonio J Guerra, Hernan Lara-Padilla, Luiz H Catalani, Matthew L Becker, Ciro A Rodriguez, David Dean
With the advent of inexpensive and highly accurate 3D printing devices, a tremendous flurry of research activity has been unleashed into new resorbable, polymeric materials that can be printed using three approaches: hydrogels for bioprinting and bioplotting, sintered polymer powders, and solid cured (photocrosslinked) resins. Additionally, there is a race to understand the role of extracellular matrix components and cell signaling molecules and to fashion ways to incorporate these materials into resorbable implants...
January 14, 2019: Current Drug Targets
Prem Prakash Tripathi, Hamed Arami, Ivneet Banga, Jalaj Gupta, Sonu Gandhi
Delivery of imaging reagents and drugs to tumors is essential for cancer diagnosis and therapy. In addition to therapeutic and diagnostic functionalities, peptides have potential benefits such as biocompatibility, ease to synthesize, smaller size, by-passing off-target side effects, and achieving the beneficial effects with lower-administered dosages. A particular type of peptide known as cell penetrating peptides (CPP) have been predominantly studied during last twenty years as they are not only capable to translocate themselves across membranes but also allow carrier drugs to translocate across plasma membrane, by different mechanisms depending on the CPP...
December 14, 2018: Oncotarget
Nitin Patil, John Karas, Bradley J Turner, Fazel Shabanpoor
Antisense oligonucleotides (ASO)-based drugs are emerging with great potential as therapeutic compounds for diseases with unmet medical needs. However, for ASOs to be effective as clinical entities, they should reach their intracellular RNA and DNA targets at pharmacologically relevant concentrations. Over the past decades various covalently attached delivery vehicles have been utilised for intracellular delivery of ASOs. One such approach is the use of biocompatible cell-penetrating peptides (CPPs) covalently conjugated to ASOs...
January 15, 2019: Bioconjugate Chemistry
Xinli Gao, Song Hong, Zhiping Liu, Tongtao Yue, Jure Dobnikar, Xianren Zhang
Cell-penetrating peptides (CPPs) are frequently employed as drug delivery agents with rapid cellular uptake, however, the uptake mechanism and the detailed translocation pathway are at present not completely understood. Both endocytosis and direct translocation through membrane pores have been observed in experiments and simulations under different conditions. Here we report the molecular dynamics simulations providing evidence for the direct translocation of CPPs across the membrane driven by the membrane electrostatic potential...
January 15, 2019: Nanoscale
Natalia Zashikhina, Vladimir Sharoyko, Mariia Antipchik, Irina Tarasenko, Yurii Anufrikov, Antonina Lavrentieva, Tatiana Tennikova, Evgenia Korzhikova-Vlakh
The development and application of novel nanospheres based on cationic and anionic random amphiphilic polypeptides with prolonged stability were proposed. The random copolymers, e.g., poly(l-lysine- co -d-phenylalanine) (P(Lys- co -dPhe)) and poly(l-glutamic acid- co -d-phenylalanine) (P(Glu- co -dPhe)), with different amount of hydrophilic and hydrophobic monomers were synthesized. The polypeptides obtained were able to self-assemble into nanospheres. Such characteristics as size, PDI and ζ-potential of the nanospheres were determined, as well as their dependence on pH was also studied...
January 11, 2019: Pharmaceutics
Sara Silva, António J Almeida, Nuno Vale
Cell-penetrating peptides (CPPs), also known as protein translocation domains, membrane translocating sequences or Trojan peptides, are small molecules of 6 to 30 amino acid residues capable of penetrating biological barriers and cellular membranes. Furthermore, CPP have become an alternative strategy to overcome some of the current drug limitations and combat resistant strains since CPPs are capable of delivering different therapeutic molecules against a wide range of diseases. In this review, we address the recent conjugation of CPPs with nanoparticles, which constitutes a new class of delivery vectors with high pharmaceutical potential in a variety of diseases...
January 10, 2019: Biomolecules
Alok Jain, Christoph Globisch, Sandeep Verma, Christine Peter
Biocompatible nanostructures play an important role in drug delivery and tissue engineering applications. A controlled growth of peptide based nanoparticles with specific morphology needs an understanding of the role of the sequence and solvation properties. In a previous combined experimental-computational study we identified factors that govern the formation of well-defined aggregates by self-assembled pentapeptides, using single amino acid substitution (Mishra, N. K.; Jain, A.; Peter, C.; Verma, S. J. Phys...
January 11, 2019: Journal of Chemical Theory and Computation
Liron L Israel, Oliver Braubach, Anna Galstyan, Antonella Chiechi, Ekaterina S Shatalova, Zachary Grodzinski, Hui Ding, Keith L Black, Julia Y Ljubimova, Eggehard Holler
One of the major problems facing the treatment of neurological disorders is the poor delivery of therapeutic agents into the brain. Our goal is to develop a multifunctional and biodegradable nanoconjugate drug delivery system that crosses the blood-brain barrier (BBB) to access brain tissues affected by neurological disease. In this study, we synthesized a biodegradable non-toxic β-poly(L-malic acid) (PMLA or P) as a scaffold to chemically bind the BBB crossing peptides Angiopep-2 (AP2), Miniap-4 (M4), and the transferrin receptor ligands cTfRL and B6...
January 11, 2019: ACS Nano
Jannet Kamoun, Renaud Rahier, Mohamed Sellami, Imed Koubaa, Pascal Mansuelle, Régine Lebrun, Alexandra Berlioz-Barbier, Michele Fiore, Karine Alvarez, Abdelkarim Abousalham, Frédéric Carrière, Ahmed Aloulou
The identification and isolation of bioactive compounds are of great interest in the drug delivery field, despite being a difficult task. We describe here an innovative strategy for the identification of a new gastric lipase inhibitor from star anise for the treatment of obesity. After plant screening assays for gastric lipase inhibition, star anise was selected and investigated by bioactivity guided fractionation. MALDI-TOF mass spectrometry and peptide mass fingerprinting allowed the detection of an inhibitor covalently bound to the catalytic serine of gastric lipase...
January 11, 2019: Food & Function
Ankur Sharma, Kalpesh Vaghasiya, Eupa Ray, Pushpa Gupta, Amit Kumar Singh, Umesh Datta Gupta, Rahul Kumar Verma
Resistance to anti-Tuberculosis (anti-TB) drugs is primarily due to unique intrinsic resistance mechanisms that mycobacterium possess. The most important determinant of resistance is a peculiar hydrophobic and multi-layered mycobacterial cell-wall structure with mycolic-acid and wax-D, which restricts permeability of both hydrophobic and hydrophilic drugs into bacteria. In this study, it was supposed that Host Defense peptides (HDP) which are known to permeabilize bacterial membranes may, therefore, help anti-TB antibiotics to target internal sites in bacteria...
January 7, 2019: International Journal of Pharmaceutics
Chune Zhu, Tingting Peng, Di Huang, Disang Feng, Xinyi Wang, Xin Pan, Wen Tan, Chuanbin Wu
Spherical poly (D, L-lactic-co-glycolic acid) microparticles (PLGA-MPs) have long been investigated in order to achieve sustained delivery of proteins/peptides. However, the formation mechanism and release characteristics of the specific shape MPs were still unknown. This study aimed to develop a novel-dimpled exenatide-loaded PLGA-MPs (Exe-PLGA-MPs) using an ultra-fine particle processing system (UPPS) and investigate the formation mechanism and release characteristics. Exe-PLGA-MPs were prepared by UPPS and optimized based on their initial burst within the first 24 h and drug release profiles...
January 9, 2019: AAPS PharmSciTech
Shantanu Guha, Jenisha Ghimire, Eric Wu, William C Wimley
Membrane permeabilizing peptides (MPPs) are as ubiquitous as the lipid bilayer membranes they act upon. Produced by all forms of life, most membrane permeabilizing peptides are used offensively or defensively against the membranes of other organisms. Just as nature has found many uses for them, translational scientists have worked for decades to design or optimize membrane permeabilizing peptides for applications in the laboratory and in the clinic ranging from antibacterial and antiviral therapy and prophylaxis to anticancer therapeutics and drug delivery...
January 9, 2019: Chemical Reviews
Zih An Chen, Sihan Wu, Peilin Chen, Yi-Ping Chen, Chung-Yuan Mou
Mesoporous silica nanoparticles (MSNs) hold great potential as a versatile platform for biomedical applications, especially drug delivery. However, evidence shows MSNs even when pegylated are rapidly cleared from the bloodstream by the monocyte phagocytic system. Erythrocytes, also called red blood cells (RBCs), can serve as biocompatible carriers of various bioactive substances, including drugs, enzymes, and peptides. In this work, we synthesize a series of fluorescent PEGylated MSNs with different synthetic diameters ranging from 10 nm to 200 nm and investigate the size effect on their encapsulation in human RBCs (hRBCs) by a hypotonic dialysis-based method...
January 9, 2019: ACS Applied Materials & Interfaces
Rachel Huey, Dan Rathbone, Paul McCarron, Susan Hawthorne
In recent years, rabies virus-derived peptide (RDP) has shown promise as a specific neural cell targeting ligand, however stability of the peptide in human serum was unknown. Herein, we report the molecular modelling and design of an optimised peptide sequence based on interactions of RDP with the α7 subunit of the nicotinic acetylcholine receptor (nAChR). The new sequence, named DAS, designed around a 5-mer sequence which demonstrated optimal nAChR binding in silico, showed greatly improved stability for up to 8 hours in human serum in comparison to RDP, which degraded within 2 hours at 37 °C...
January 9, 2019: Journal of Drug Targeting
Sohameh Mohebbi, Tahereh Tohidi Moghadam, Maryam Nikkhah, Mehrdad Behmanesh
Gold nanorods (GNRs) have been nominated as a promising candidate for a variety of biological applications; however, the cationic surfactant layer that surrounds a nanostructure places limits on its biological applicability. Herein, CTAB-GNRs were functionalized via a ligand exchange method using a (C(HK)4-mini PEG-RGD)-peptide to target the overexpressed αvβ3 integrin in cancerous cells, increase the biocompatibility, and gain the ability of gene/drug delivery, simultaneously. To confirm an acceptable functionalization, UV-Visible, FTIR, and Raman spectroscopy, zeta potential, and transmission electron microscopy of nanostructures were done...
January 8, 2019: Nanoscale Research Letters
K Rasheeda, Charuvaka Muvva, Nishad Fathima Nishter
Collagen type I a fibrous protein, is highly biocompatible, biodegradable and exhibits low immunogenicity with its unique feature of undergoing spontaneous self-assembly process. However, the excessive accumulation of collagen may lead to a condition known as fibrosis in a higher form of vertebrates. Plant alkaloids have gained much attention in recent years as the biomedical and therapeutic agents. Therefore, drawing inspiration from the biological and structural tunability of these alkaloids, this work aims to inhibit the self-assembly of type I collagen using (±)-Alpha-lipoic acid (ALA)...
January 9, 2019: Langmuir: the ACS Journal of Surfaces and Colloids
Tatiana Radchenko, Fabien Fontaine, Luca Morettoni, Ismael Zamora
Peptide drugs have been used in the treatment of multiple pathologies. During peptide discovery, it is crucially important to be able to map the potential sites of cleavages of the proteases. This knowledge is used to later chemically modify the peptide drug to adapt it for the therapeutic use, making peptide stable against individual proteases or in complex medias. In some other cases it needed to make it specifically unstable for some proteases, as peptides could be used as a system to target delivery drugs on specific tissues or cells...
2019: PloS One
Erica B Peters, Nick D Tsihlis, Mark R Karver, Stacey M Chin, Bruno Musetti, Benjamin T Ledford, Edward M Bahnson, Samuel I Stupp, Melina R Kibbe
Nanomedicine is a promising, noninvasive approach to reduce atherosclerotic plaque burden. However, drug delivery is limited without the ability of nanocarriers to sense and respond to the diseased microenvironment. In this study, nanomaterials are developed from peptide amphiphiles (PAs) that respond to the increased levels of matrix metalloproteinases 2 and 9 (MMP2/9) or reactive oxygen species (ROS) found within the atherosclerotic niche. A pro-resolving therapeutic, Ac2-26, derived from annexin-A1 protein, is tethered to PAs using peptide linkages that cleave in response to MMP2/9 or ROS...
January 8, 2019: Advanced Healthcare Materials
Sebastien Benizri, Arnaud Gissot, Andrew Martin, Brune Vialet, Philippe Barthelemy, Mark W Grinstaff
Oligonucleotide-based agents have the potential to treat or cure almost any disease, and are one of the key therapeutic drug classes of the future. Bioconjugated oligonucleotides, a subset of this class, are emerging from basic research and being successfully translated to the clinic. In this review, we first briefly describe two approaches for inhibiting specific genes using oligonucleotides - antisense DNA (ASO) and RNA interference (RNAi) - followed by a discussion on delivery to cells. We then summarize and analyze recent developments in bioconjugated oligonucleotides including those possessing GalNAc, cell penetrating peptides, α-tocopherol, aptamers, antibodies, cholesterol, squalene, fatty acids, or nucleolipids...
January 4, 2019: Bioconjugate Chemistry
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