The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Zhen Gu - One of the best experts on this subject based on the ideXlab platform.
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polymeric microneedles for transdermal Protein Delivery
Advanced Drug Delivery Reviews, 2018Co-Authors: Yanqi Ye, Jicheng Yu, Anna R Kahkoska, Zhen GuAbstract:Abstract The intrinsic properties of therapeutic Proteins generally present a major impediment for transdermal Delivery, including their relatively large molecule size and susceptibility to degradation. One solution is to utilize microneedles (MNs), which are capable of painlessly traversing the stratum corneum and directly translocating Protein drugs into the systematic circulation. MNs can be designed to incorporate appropriate structural materials as well as therapeutics or formulations with tailored physicochemical properties. This platform technique has been applied to deliver drugs both locally and systemically in applications ranging from vaccination to diabetes and cancer therapy. This review surveys the current design and use of polymeric MNs for transdermal Protein Delivery. The clinical potential and future translation of MNs are also discussed.
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redox responsive nanocapsules for intracellular Protein Delivery
Biomaterials, 2011Co-Authors: Muxun Zhao, Anuradha Biswas, Biliang Hu, Zhen Gu, Pin Wang, Yi TangAbstract:Direct Delivery of Proteins to the cytosol of cells holds tremendous potential in biological and medical applications. Engineering vehicles for escorting Proteins to the cytosol in a controlled release fashion has thus generated considerable interest. We report here the preparation of redox-responsive single-Protein nanocapsules for intracellular Protein Delivery. Through in situ interfacial polymerization, the target Protein is noncovalently encapsulated into a positively-charged polymeric shell interconnected by disulfide-containing crosslinkers. The dissociation of the polymeric shell under reducing conditions and the subsequent release of Protein were confirmed using cell-free assays in the presence of glutathione (GSH). The nanocapsules were demonstrated to be efficiently internalized into the cells and to release the Protein in the reducing cytosol. Using the nanocapsule as a vehicle, we showed that active caspase 3 (CP-3) can be delivered and can induce apoptosis in a variety of human cancer cell lines, including HeLa, MCF-7 and U-87 MG. Our approach therefore presents an effective intracellular Protein Delivery strategy for therapeutic, diagnostic and reprogramming applications.
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a novel intracellular Protein Delivery platform based on single Protein nanocapsules
Nature Nanotechnology, 2010Co-Authors: Juanjuan Du, Zhen Gu, Min Liang, Yufang Hu, Wenjun Zhang, Saul J Priceman, Lily Wu, Hong Z Zhou, Tatiana Segura, Yi TangAbstract:An average cell contains thousands of Proteins that participate in normal cellular functions, and most diseases are somehow related to the malfunctioning of one or more of these Proteins. Protein therapy1, which delivers Proteins into the cell to replace the dysfunctional Protein, is considered the most direct and safe approach for treating disease. However, the effectiveness of this method has been limited by its low Delivery efficiency and poor stability against proteases in the cell, which digest the Protein. Here, we show a novel Delivery platform based on nanocapsules consisting of a Protein core and a thin permeable polymeric shell that can be engineered to either degrade or remain stable at different pHs. Non-degradable capsules show long-term stability, whereas the degradable ones break down their shells, enabling the core Protein to be active once inside the cells. Multiple Proteins can be delivered to cells with high efficiency while maintaining low toxicity, suggesting potential applications in imaging, therapy and cosmetics fields. Nanocapsules with polymeric shells can effectively deliver Proteins into cells to trigger the activity of its substrates that are inside the cells.
Shouguang Jin - One of the best experts on this subject based on the ideXlab platform.
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bacterial type iii secretion system as a Protein Delivery tool for a broad range of biomedical applications
Biotechnology Advances, 2018Co-Authors: Fang Bai, Akihiro Umezawa, Naohiro Terada, Shouguang JinAbstract:A Protein Delivery tool based on bacterial type III secretion system (T3SS) has been broadly applied in biomedical researches. In this review, we summarize various applications of the T3SS-mediate Protein Delivery which enables translocation of Proteins directly into mammalian cells without Protein purification. Some of the remarkable advancements include Delivery of antigens for therapeutic vaccines, nucleases for genome editing, transcription factors for cellular reprogramming and stem cells differentiation, and signaling molecules for post-translational proteomics studies. With continued improvement of the T3SS-mediated Protein Delivery tools, even wider application of the technology is anticipated.
Kinam Park - One of the best experts on this subject based on the ideXlab platform.
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nanoparticles for oral Delivery targeted nanoparticles with peptidic ligands for oral Protein Delivery
Advanced Drug Delivery Reviews, 2013Co-Authors: Yeonhee Yun, Yong Woo Cho, Kinam ParkAbstract:As the field of biotechnology has advanced, oral Protein Delivery has also made significant progress. Oral Delivery is the most common method of drug administration with high levels of patient acceptance. Despite the preference of oral Delivery, administration of therapeutic Proteins has been extremely difficult. Increasing the bioavailability of oral Protein drugs to the therapeutically acceptable level is still a challenging goal. Poor membrane permeability, high molecular weight, and enzymatic degradation of Protein drugs have remained unsolved issues. Among diverse strategies, nanotechnology has provided a glimpse of hope in oral Delivery of Protein drugs. Nanoparticles have advantages, such as small size, high surface area, and modification using functional groups for high capacity or selectivity. Nanoparticles with peptidic ligands are especially worthy of notice because they can be used for specific targeting in the gastrointestinal (GI) tract. This article reviews the transport mechanism of the GI tract, barriers to Protein absorption, current status and limitations of nanotechnology for oral Protein Delivery system.
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issues in long term Protein Delivery using biodegradable microparticles
Journal of Controlled Release, 2010Co-Authors: Sungwon Kim, Kinam ParkAbstract:Abstract Recently, a variety of bioactive Protein drugs have been available in large quantities as a result of advances in biotechnology. Such availability has prompted development of long-term Protein Delivery systems. Biodegradable microparticulate systems have been used widely for controlled release of Protein drugs for days and months. The most widely used biodegradable polymer has been poly( d , l -lactic-co-glycolic acid) (PLGA). Protein-containing microparticles are usually prepared by the water/oil/water (W/O/W) double emulsion method, and variations of this method, such as solid/oil/water (S/O/W) and water/oil/oil (W/O/O), have also been used. Other methods of preparation include spray drying, ultrasonic atomization, and electrospray methods. The important factors in developing biodegradable microparticles for Protein drug Delivery are Protein release profile (including burst release, duration of release, and extent of release), microparticle size, Protein loading, encapsulation efficiency, and bioactivity of the released Protein. Many studies used albumin as a model Protein, and thus, the bioactivity of the release Protein has not been examined. Other studies which utilized enzymes, insulin, erythropoietin, and growth factors have suggested that the right formulation to preserve bioactivity of the loaded Protein drug during the processing and storage steps is important. The Protein release profiles from various microparticle formulations can be classified into four distinct categories (Types A, B, C, and D). The categories are based on the magnitude of burst release, the extent of Protein release, and the Protein release kinetics followed by the burst release. The Protein loading (i.e., the total amount of Protein loaded divided by the total weight of microparticles) in various microparticles is 6.7 ± 4.6%, and it ranges from 0.5% to 20.0%. Development of clinically successful long-term Protein Delivery systems based on biodegradable microparticles requires improvement in the drug loading efficiency, control of the initial burst release, and the ability to control the Protein release kinetics.
Jorge E Galan - One of the best experts on this subject based on the ideXlab platform.
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bacterial type iii secretion systems specialized nanomachines for Protein Delivery into target cells
Annual Review of Microbiology, 2014Co-Authors: Jorge E Galan, Maria Laratejero, Thomas C Marlovits, Samuel WagnerAbstract:One of the most exciting developments in the field of bacterial pathogenesis in recent years is the discovery that many pathogens utilize complex nanomachines to deliver bacterially encoded effector Proteins into target eukaryotic cells. These effector Proteins modulate a variety of cellular functions for the pathogen's benefit. One of these Protein-Delivery machines is the type III secretion system (T3SS). T3SSs are widespread in nature and are encoded not only by bacteria pathogenic to vertebrates or plants but also by bacteria that are symbiotic to plants or insects. A central component of T3SSs is the needle complex, a supramolecular structure that mediates the passage of the secreted Proteins across the bacterial envelope. Working in conjunction with several cytoplasmic components, the needle complex engages specific substrates in sequential order, moves them across the bacterial envelope, and ultimately delivers them into eukaryotic cells. The central role of T3SSs in pathogenesis makes them great t...
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bacterial type iii secretion systems specialized nanomachines for Protein Delivery into target cells
Annual Review of Microbiology, 2014Co-Authors: Jorge E Galan, Maria Laratejero, Thomas C Marlovits, Samuel WagnerAbstract:One of the most exciting developments in the field of bacterial pathogenesis in recent years is the discovery that many pathogens utilize complex nanomachines to deliver bacterially encoded effector Proteins into target eukaryotic cells. These effector Proteins modulate a variety of cellular functions for the pathogen's benefit. One of these Protein-Delivery machines is the type III secretion system (T3SS). T3SSs are widespread in nature and are encoded not only by bacteria pathogenic to vertebrates or plants but also by bacteria that are symbiotic to plants or insects. A central component of T3SSs is the needle complex, a supramolecular structure that mediates the passage of the secreted Proteins across the bacterial envelope. Working in conjunction with several cytoplasmic components, the needle complex engages specific substrates in sequential order, moves them across the bacterial envelope, and ultimately delivers them into eukaryotic cells. The central role of T3SSs in pathogenesis makes them great targets for novel antimicrobial strategies.
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Protein Delivery into eukaryotic cells by type iii secretion machines
Nature, 2006Co-Authors: Jorge E Galan, Hans WolfwatzAbstract:Bacteria that have sustained long-standing close associations with eukaryotic hosts have evolved specific adaptations to survive and replicate in this environment. Perhaps one of the most remarkable of those adaptations is the type III secretion system (T3SS)--a bacterial organelle that has specifically evolved to deliver bacterial Proteins into eukaryotic cells. Although originally identified in a handful of pathogenic bacteria, T3SSs are encoded by a large number of bacterial species that are symbiotic or pathogenic for humans, other animals including insects or nematodes, and plants. The study of these systems is leading to unique insights into not only organelle assembly and Protein secretion but also mechanisms of symbiosis and pathogenesis.
Samuel Wagner - One of the best experts on this subject based on the ideXlab platform.
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bacterial type iii secretion systems specialized nanomachines for Protein Delivery into target cells
Annual Review of Microbiology, 2014Co-Authors: Jorge E Galan, Maria Laratejero, Thomas C Marlovits, Samuel WagnerAbstract:One of the most exciting developments in the field of bacterial pathogenesis in recent years is the discovery that many pathogens utilize complex nanomachines to deliver bacterially encoded effector Proteins into target eukaryotic cells. These effector Proteins modulate a variety of cellular functions for the pathogen's benefit. One of these Protein-Delivery machines is the type III secretion system (T3SS). T3SSs are widespread in nature and are encoded not only by bacteria pathogenic to vertebrates or plants but also by bacteria that are symbiotic to plants or insects. A central component of T3SSs is the needle complex, a supramolecular structure that mediates the passage of the secreted Proteins across the bacterial envelope. Working in conjunction with several cytoplasmic components, the needle complex engages specific substrates in sequential order, moves them across the bacterial envelope, and ultimately delivers them into eukaryotic cells. The central role of T3SSs in pathogenesis makes them great t...
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bacterial type iii secretion systems specialized nanomachines for Protein Delivery into target cells
Annual Review of Microbiology, 2014Co-Authors: Jorge E Galan, Maria Laratejero, Thomas C Marlovits, Samuel WagnerAbstract:One of the most exciting developments in the field of bacterial pathogenesis in recent years is the discovery that many pathogens utilize complex nanomachines to deliver bacterially encoded effector Proteins into target eukaryotic cells. These effector Proteins modulate a variety of cellular functions for the pathogen's benefit. One of these Protein-Delivery machines is the type III secretion system (T3SS). T3SSs are widespread in nature and are encoded not only by bacteria pathogenic to vertebrates or plants but also by bacteria that are symbiotic to plants or insects. A central component of T3SSs is the needle complex, a supramolecular structure that mediates the passage of the secreted Proteins across the bacterial envelope. Working in conjunction with several cytoplasmic components, the needle complex engages specific substrates in sequential order, moves them across the bacterial envelope, and ultimately delivers them into eukaryotic cells. The central role of T3SSs in pathogenesis makes them great targets for novel antimicrobial strategies.