The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Jing Wang - One of the best experts on this subject based on the ideXlab platform.
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synthesis of dual key and lock Drug Carriers for imaging and improved Drug release
Nanotechnology, 2020Co-Authors: Haiqing Gao, Yongqi Zhang, Bin Chi, Caixue Lin, Feng Tian, Yingxi Wang, Jing WangAbstract:In this work, a 'dual-key-and-lock' Drug carrier was designed to respond to the tumor microenvironment (TME). A core-shell Fe-MOF@ZIF-8 was synthesized, with ZIF-8 as the shell (the first lock) to encapsulate catalase (CAT), and the Fe metal-organic framework (MOF) as the core (the second lock) to encapsulate the anticancer Drug doxorubicin (DOX). Fe-MOF@ZIF-8 takes advantage of the TME-which includes a high concentration of H2O2, a weakly acidic environment and hypoxia-to achieve efficient cancer therapy. With the pH response, ZIF-8 and Fe-MOF are degraded in turn to release CAT and DOX, just like 'pH stimulation', as a key to open the two locks in turn. The released CAT reacts with the rich H2O2 in the tumor to produce O2 to regulate hypoxia, thereby improving the anticancer efficiency of the released DOX. The different cytotoxicity to L-02 cells and HeLa cells of Fe-MOF@ZIF-8 shows Fe-MOF@ZIF-8 is only harmful to cancer cells and is not harmful to normal cells. The reason is that the Fe2+/Fe3+ in Fe-MOF interact with the rich H2O2 in cancer cells to generate hydroxyl radicals (ċOH), which is proved by the color of the solution of 3,3',5,5'-tetramethylbenzidine turning blue. After loading of the Drug and CAT, Fe-MOF@ZIF-8 can release CAT, DOX and ċOH in response to the TME, thus killing more HeLa cells. Therefore, synthesis of 'dual-key-and-lock' Drug Carriers responsive to the TME is a promising strategy for cancer treatment.
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construction dual key and lock Drug Carriers for imaging and improved Drug release
Nanotechnology, 2020Co-Authors: Haiqing Gao, Yongqi Zhang, Bin Chi, Caixue Lin, Feng Tian, Yingxi Wang, Jing WangAbstract:In this work, a "dual-key and-Lock" Drug carrier was designed to respond to tumor microenvironment. A core-shell Fe-MOF@ZIF-8 was synthesized, with ZIF-8 as shell (the first lock) to encapsulate catalase, Fe-MOF as core (the second lock) to encapsulate anticancer Drug doxorubicin (DOX). Fe-MOs@ZIF-8 takes advantage of tumor microenvironment includes high concentration of H2O2, weak acidic environment and hypoxia to achieve efficient cancer therapy. With the pH response, the ZIF-8 and the Fe-MOF will be degraded in turn to release catalase and DOX, just like "pH stimulation" as a key to open two locks in turn. The released catalase reacts with rich H2O2 in tumor to produce O2 to regulate hypoxia, thereby improving the anti-cancer efficiency of released DOX. The different cytotoxicity to L-02 cells and HeLa cells of Fe-MOF@ZIF-8 shows Fe-MOF@ZIF-8 is only harmful to cancer cells and not harmful to normal cells. The reason is that the Fe2+/Fe3+ in Fe-MOF interact with rich H2O2 in cancer cells to generate hydroxyl radicals (âOH), which is proved by the color of the solution of 3,3',5,5'-tetramethylbenzidine turns blue. After loading the Drug and catalase, Fe-MOF@ZIF-8 can release catalase, DOX and âOH in response to tumor microenvironment, thus killing more Hela cells. Therefore, construction of "Dual-Key-and-Lock" Drug Carriers respond to tumor microenvironment are a promising strategy for cancer treatment.
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alpcs 4 pdt for gastric cancer therapy using gold nanorod cationic liposome and pluronic f127 nanomicellar Drug Carriers
International Journal of Nanomedicine, 2018Co-Authors: Jing Xin, Sijia Wang, Bing Wang, Jiazhuang Wang, Jing Wang, Luwei Zhang, Bo Xin, Lijian Shen, Zhenxi Zhang, Cuiping YaoAbstract:Purpose As a promising photodynamic therapy (PDT) agent, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) provides deep penetration into tissue, high quantum yields, good photostability, and low photobleaching. However, its low delivery efficiency and high binding affinity to serum albumin cause its low penetration into cancer cells, further limiting its PDT effect on gastric cancer. In order to improve AlPcS4/PDT effect, the AlPcS4 delivery sys tems with different Drug Carriers were synthesized and investigated. Materials and methods Gold nanorods, cationic liposomes, and Pluronic® F127 nanomicellars were used to formulate the AlPcS4 delivery systems. The anticancer effect was evaluated by CCK-8 assay and colony formation assay. The delivery efficiency of AlPcS4 and the binding affinity to serum proteins were determined by fluorescence intensity assay. The apoptosis and necrosis ability, reactive oxygen species and singlet oxygen generation, mitochondrial transmembrane potential and ([Ca2+]i) concentration were further measured to evaluate the mechanism of cell death. Results The series of synthesized AlPcS4 delivery systems with different Drug Carriers improve the limited PDT effect in varying degrees. In contrast, AlPcS4 complex with gold nanorods has significant anticancer effects because gold nanorods are not only suitable for AlPcS4 delivery, but also exhibit enhanced singlet oxygen generation effect and photothermal effect to induce cell death directly. Moreover, AlPcS4 complex with cationic liposomes shows the potent inhibition effect because of its optimal AlPcS4 delivery efficiency and ability to block serum albumin. In addition, AlPcS4 complex with Pluronic F127 exhibits inferior PDT effect but presents lower cytotoxicity, slower dissociation rate, and longer retention time of incorporated Drugs; thus, F127-AlPcS4 is used for prolonged gastric cancer therapy. Conclusion The described AlPcS4 Drug delivery systems provide promising agents for gastric cancer therapy.
Gregor Cevc - One of the best experts on this subject based on the ideXlab platform.
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lipid vesicles and other colloids as Drug Carriers on the skin
Advanced Drug Delivery Reviews, 2004Co-Authors: Gregor CevcAbstract:Abstract Colloids from an aqueous suspension can cross the skin barrier only through hydrophilic pathways. Various colloids have a different ability to do this by penetrating narrow pores of fixed size in the skin, or the relevant nano-pores in barriers modelling the skin. Such ability is governed by colloid adaptability, which must be high enough to allow penetrant deformation to the size of a pore in such barrier: for a 100 nm colloid trespassing the skin this means at least 5-fold deformation/elongation. (Lipid) Bilayer vesicles are normally more adaptable than the comparably large (lipid coated) fluid droplets. One of the reasons for this, and an essential condition for achieving a high bilayer adaptability and pore penetration, is a high bilayer membrane elasticity. The other reason is the relaxation of changing colloid's volume-to-surface constraint during pore penetration; it stands to reason that such relaxation requires a concurrent, but only transient and local, bilayer permeabilisation. Both these phenomena are reflected in bilayer composition sensitivity, which implies non-linear pressure dependency of the apparent barrier penetrability, for example. Amphipats that acceptably weaken a membrane (surfactants, (co)solvents, such as certain alcohols, etc.) consequently facilitate controlled, local bilayer destabilisation and increase lipid bilayer flexibility. When used in the right quantity, such additives thus lower the energetic expense for elastic bilayer deformation, associated with pore penetration. Another prerequisite for aggregate transport through the skin is the colloid-induced opening of the originally very narrow (∼0.4 nm) gaps between cells in the barrier to pores with diameter above 30 nm. Colloids incapable of enforcing such widening—and simultaneously of self-adapting to the size of 20–30 nm without destruction—are confined to the skin surface. All relatively compact colloids seem to fall in this latter category. This includes mixed lipid micelles, solid (nano)particles, nano-droplets, biphasic vesicles, etc. Such colloids, therefore, merely enter the skin through the rare wide gaps between groups of skin cells near the organ surface. Transdermal Drug delivery systems based on corresponding Drug formulations, therefore, rely on simple Drug diffusion through the skin; the colloid then, at best, can modulate Drug transport through the barrier. In contrast, the adaptability-and stability-optimised mixed lipid vesicles (Transfersomes®, a trademark of IDEA AG) can trespass much narrower pathways between most cells in the skin; such highly adaptable colloids thus mediate Drug transport through the skin. Sufficiently stable ultra-adaptable Carriers, therefore, can ensure targeted Drug delivery deep below the application site. This has already been shown in numerous preclinical tests and several phase I and phase II clinical studies. Drug delivery by means of highly adaptable Drug Carriers, moreover, allows highly efficient and well-tolerated Drug targeting into the skin proper. Sustained Drug release through the skin into systemic blood circulation is another field of ultradeformable Drug carrier application.
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lipid vesicles and other colloids as Drug Carriers on the skin
Advanced Drug Delivery Reviews, 2004Co-Authors: Gregor CevcAbstract:Colloids from an aqueous suspension can cross the skin barrier only through hydrophilic pathways. Various colloids have a different ability to do this by penetrating narrow pores of fixed size in the skin, or the relevant nano-pores in barriers modelling the skin. Such ability is governed by colloid adaptability, which must be high enough to allow penetrant deformation to the size of a pore in such barrier: for a 100 nm colloid trespassing the skin this means at least 5-fold deformation/elongation. (Lipid) Bilayer vesicles are normally more adaptable than the comparably large (lipid coated) fluid droplets. One of the reasons for this, and an essential condition for achieving a high bilayer adaptability and pore penetration, is a high bilayer membrane elasticity. The other reason is the relaxation of changing colloid's volume-to-surface constraint during pore penetration; it stands to reason that such relaxation requires a concurrent, but only transient and local, bilayer permeabilisation. Both these phenomena are reflected in bilayer composition sensitivity, which implies non-linear pressure dependency of the apparent barrier penetrability, for example. Amphipats that acceptably weaken a membrane (surfactants, (co)solvents, such as certain alcohols, etc.) consequently facilitate controlled, local bilayer destabilisation and increase lipid bilayer flexibility. When used in the right quantity, such additives thus lower the energetic expense for elastic bilayer deformation, associated with pore penetration. Another prerequisite for aggregate transport through the skin is the colloid-induced opening of the originally very narrow ( approximately 0.4 nm) gaps between cells in the barrier to pores with diameter above 30 nm. Colloids incapable of enforcing such widening-and simultaneously of self-adapting to the size of 20-30 nm without destruction-are confined to the skin surface. All relatively compact colloids seem to fall in this latter category. This includes mixed lipid micelles, solid (nano)particles, nano-droplets, biphasic vesicles, etc. Such colloids, therefore, merely enter the skin through the rare wide gaps between groups of skin cells near the organ surface. Transdermal Drug delivery systems based on corresponding Drug formulations, therefore, rely on simple Drug diffusion through the skin; the colloid then, at best, can modulate Drug transport through the barrier. In contrast, the adaptability-and stability-optimised mixed lipid vesicles (Transfersomes, a trademark of IDEA AG) can trespass much narrower pathways between most cells in the skin; such highly adaptable colloids thus mediate Drug transport through the skin. Sufficiently stable ultra-adaptable Carriers, therefore, can ensure targeted Drug delivery deep below the application site. This has already been shown in numerous preclinical tests and several phase I and phase II clinical studies. Drug delivery by means of highly adaptable Drug Carriers, moreover, allows highly efficient and well-tolerated Drug targeting into the skin proper. Sustained Drug release through the skin into systemic blood circulation is another field of ultradeformable Drug carrier application.
Rainer H. Müller - One of the best experts on this subject based on the ideXlab platform.
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influence of surface charge density on protein adsorption on polymeric nanoparticles analysis by two dimensional electrophoresis
European Journal of Pharmaceutics and Biopharmaceutics, 2002Co-Authors: Andrea Gessner, Antje Lieske, Berndr Paulke, Rainer H. MüllerAbstract:Plasma protein adsorption is regarded as a key factor for the in vivo organ distribution of intravenously administered colloidal Drug Carriers, and strongly depends on their surface characteristics, e.g. surface hydrophobicity or charge. A range of polymeric nanoparticles with a steep variation of the surface charge density was synthesized as model Drug Carriers. Physicochemical parameters, i.e. particle size, surface charge density, hydrophobicity and surface topography were determined. Two-dimensional electrophoresis (2-DE) was employed for determination of particle interactions with human plasma proteins. Increasing surface charge density showed an increase in plasma protein adsorption, but did not show differences in the detected protein species. For the first time it was possible to show plasma protein adsorption patterns on a range of nanoparticles with variation of only one parameter, i.e. the charge, while size and surface hydrophobicity remain practically unchanged. The knowledge about the interactions of proteins with particulate surfaces can be exploited for the future controlled design of colloidal Drug Carriers and possibly in the controlled creation of biocompatible surfaces of other devices that come into contact with proteins (e.g. microparticles and implants).
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analysis of plasma protein adsorption on polymeric nanoparticles with different surface characteristics
Journal of Biomedical Materials Research, 1998Co-Authors: Martin Luck, Berndr Paulke, Werner Schroder, T Blunk, Rainer H. MüllerAbstract:Plasma protein adsorption patterns on colloidal Drug Carriers acquired after iv administration depend on their surface characteristics and are regarded as key factors for their in vivo organ distribution. Polymeric latex particles with strongly differing surface properties were synthesized as models for colloidal Drug Carriers for tissue-specific Drug targeting via the intravenous route. Physicochemical char- acterization was performed for size, surface charge density, zeta potential, and surface hydrophobicity. The interactions with human plasma proteins were studied by way of two- dimensional polyacrylamide gel electrophoresis (2-D PAGE). Considerable differences in protein adsorption on the latex particles were detected with regard to the total amount of surface-bound protein on the various particle types as well as specific proteins adsorbed, for example, fibrinogen, albumin, and a recently identified plasma glyco- protein. Possible correlations between protein adsorption patterns and the physicochemical characteristics and topog- raphy of the polymeric surfaces are shown and discussed. Knowledge about protein-nanoparticle interactions can be utilized for the rational design of colloidal Drug Carriers and also may be useful for optimizing implants and medical devices. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 478-485, 1998.
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alkylcyanoacrylate Drug Carriers ii cytotoxicity of cyanoacrylate nanoparticles with different alkyl chain length
International Journal of Pharmaceutics, 1992Co-Authors: C Lherm, Rainer H. Müller, F Puisieux, Patrick CouvreurAbstract:Abstract The cytotoxicity of four types of alkylcyanoacrylate particles was evaluated in L929 fibroblast cell cultures. The results revealed the ethyl- and isobutyl-derivatives to be the most toxic, the methyl-derivative to be of intermediated toxicity and the isohexyl-cyanoacrylate particles to have the lowest toxicity. The toxic effect was found to be correlated with the velocity of polymer degradation and the rate of release of the degradation products. The mechanism proposed to account for the observed cytotoxicity consists of the degradation of particles in the culture medium and/or of particles adhering to or in close proximity with the cell membrane. A contribution due to the internalization of particles by cells appeared to be negligible, if any, in the cytotoxicity of nanoparticles. Acute toxicity can be avoided by employing low doses of particles consisting of a slowly degrading cyanoacrylate polymer. This aspect is of interest in the development of a colloidal carrier for the chronic delivery of Drugs. The use of such systems does not involve problems as a result of long-term toxicity during chronic treatments and the burden placed upon the body by overloading with polymeric Drug Carriers that undergo degradation more slowly, such as poly(hydroxybutyric acid) and poly(lactic acid).
Rs Blumenthal - One of the best experts on this subject based on the ideXlab platform.
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Lipid-Based Nanoparticles as Pharmaceutical Drug Carriers: From Concepts to Clinic
Critical Reviews in Therapeutic Drug Carrier Systems, 2009Co-Authors: Anu Puri, Brandon Smith, Eliahu Heldman, Amichai Yavlovich, Kristin Loomis, Jae-ho Lee, Rs BlumenthalAbstract:In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical Drug Carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nanoemulsions, dendrimers, nano-gold, liposomes, Drug-carrier conjugates, antibody-Drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, Drug loading efficiencies, Drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and Drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in Drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as Drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid Carriers will be presented. We conclude with a few examples of clinically successful formulations of currently available lipid-based nanoparticles.
Cuiping Yao - One of the best experts on this subject based on the ideXlab platform.
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alpcs 4 pdt for gastric cancer therapy using gold nanorod cationic liposome and pluronic f127 nanomicellar Drug Carriers
International Journal of Nanomedicine, 2018Co-Authors: Jing Xin, Sijia Wang, Bing Wang, Jiazhuang Wang, Jing Wang, Luwei Zhang, Bo Xin, Lijian Shen, Zhenxi Zhang, Cuiping YaoAbstract:Purpose As a promising photodynamic therapy (PDT) agent, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) provides deep penetration into tissue, high quantum yields, good photostability, and low photobleaching. However, its low delivery efficiency and high binding affinity to serum albumin cause its low penetration into cancer cells, further limiting its PDT effect on gastric cancer. In order to improve AlPcS4/PDT effect, the AlPcS4 delivery sys tems with different Drug Carriers were synthesized and investigated. Materials and methods Gold nanorods, cationic liposomes, and Pluronic® F127 nanomicellars were used to formulate the AlPcS4 delivery systems. The anticancer effect was evaluated by CCK-8 assay and colony formation assay. The delivery efficiency of AlPcS4 and the binding affinity to serum proteins were determined by fluorescence intensity assay. The apoptosis and necrosis ability, reactive oxygen species and singlet oxygen generation, mitochondrial transmembrane potential and ([Ca2+]i) concentration were further measured to evaluate the mechanism of cell death. Results The series of synthesized AlPcS4 delivery systems with different Drug Carriers improve the limited PDT effect in varying degrees. In contrast, AlPcS4 complex with gold nanorods has significant anticancer effects because gold nanorods are not only suitable for AlPcS4 delivery, but also exhibit enhanced singlet oxygen generation effect and photothermal effect to induce cell death directly. Moreover, AlPcS4 complex with cationic liposomes shows the potent inhibition effect because of its optimal AlPcS4 delivery efficiency and ability to block serum albumin. In addition, AlPcS4 complex with Pluronic F127 exhibits inferior PDT effect but presents lower cytotoxicity, slower dissociation rate, and longer retention time of incorporated Drugs; thus, F127-AlPcS4 is used for prolonged gastric cancer therapy. Conclusion The described AlPcS4 Drug delivery systems provide promising agents for gastric cancer therapy.
