Jinzhong Wang | Merck - Academia.edu (original) (raw)

Papers by Jinzhong Wang

Research paper thumbnail of Comparison of PEG chain length and density on amphiphilic macromolecular nanocarriers: Self-assembled and unimolecular micelles

Acta Biomaterialia, 2009

Two classes of amphiphilic macromolecules were evaluated for drug delivery applications: those th... more Two classes of amphiphilic macromolecules were evaluated for drug delivery applications: those that exist as unimolecular micelles and those that self-assemble in aqueous solution to form micelles. This study compares the poly(ethylene glycol) (PEG) chain length and density that constitute the corona of both classes. In particular, the effect of PEG branching on micellar size, water-solubility, resolubilization rate, drug loading efficiency and drug release rate were analyzed. Pluronic P85 and Cremophor EL, commonly used in pharmaceutical applications, were used as controls. Indomethacin (IMC) was used as the drug for encapsulation, release and resolubilization experiments. Results indicated that smaller micellar sizes, higher water solubilities and faster resolubilization rates were achieved from higher PEG densities compared to linear PEG analog of similar mass. Further, micellar sizes of both higher density PEG and linear PEG macromolecules were constant over a wide temperature range (2-70 degrees C). In contrast, Cremophor EL formed aggregates at 15 degrees C and Pluronic P85 underwent a size transition at 45 degrees C. IMC loading efficiencies for all amphiphilic macromolecules were comparable to controls. However, faster resolubilization and slower drug release were observed for higher density PEG macromolecules compared to linear PEG analogs and controls.

Research paper thumbnail of Engineered Polymeric Nanoparticles for Receptor-Targeted Blockage of Oxidized Low Density Lipoprotein Uptake and Atherogenesis in Macrophages

Biomacromolecules, 2006

Strategies to prevent the uptake of modified low density lipoproteins (LDLs) by immune cells, a m... more Strategies to prevent the uptake of modified low density lipoproteins (LDLs) by immune cells, a major trigger of inflammation and atherogenesis, are challenged by complex interfacial factors governing LDL receptor-mediated uptake. We examine a new approach based on a family of "nanoblockers", which are designed to examine the role of size, charge presentation, and architecture on inhibition of highly oxidized LDL (hoxLDL) uptake in macrophages. The nanoblockers are macromolecules containing mucic acid, lauryl chloride, and poly(ethylene glycol) that self-assemble into 15-20 nm nanoparticles. We report that the micellar configuration of the macromolecules and the combined display of anionic (carboxylate) groups in the hydrophobic region of the nanoblockers caused the most effective inhibition in the uptake of hoxLDL by IC21 macrophages. The nanoblockers primarily targeted SR-A and CD36, the major scavenger receptors and modulated the "atherogenic" phenotype of cells in terms of the degree of cytokine secretion, accumulation of cholesterol, and "foam cell" formation. These studies highlight the promise of synthetically engineered nanoblockers against oxidized LDL uptake.

Research paper thumbnail of Amphiphilic Scorpion-like Macromolecules as Micellar Nanocarriers

Journal of Bioactive and Compatible Polymers, 2008

... DOI: 10.1177/0883911508097498 2008 23: 532 Journal of Bioactive and Compatible Polymers Jelen... more ... DOI: 10.1177/0883911508097498 2008 23: 532 Journal of Bioactive and Compatible Polymers Jelena Djordjevic, Leilani S. Del Rosario, Jinzhong Wang and Kathryn E. Uhrich Amphiphilic Scorpion-like Macromolecules as Micellar Nanocarriers Published by: ...

Research paper thumbnail of Local Polarity and Microviscosity in the Hydrophobic Cores of Amphiphilic Starlike and Scorpion-like Macromolecules

Macromolecules, 2007

... Karen E. Steege, Jinzhong Wang, Kathryn E. Uhrich,* and Edward W. Castner, Jr.*. Department o... more ... Karen E. Steege, Jinzhong Wang, Kathryn E. Uhrich,* and Edward W. Castner, Jr.*. Department of Chemistry and Chemical Biology Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey 08854-8087. ...

Research paper thumbnail of Dual use of amphiphilic macromolecules as cholesterol efflux triggers and inhibitors of macrophage athero-inflammation

Biomaterials, 2011

Activated vascular wall macrophages can rapidly internalize modified lipoproteins and escalate th... more Activated vascular wall macrophages can rapidly internalize modified lipoproteins and escalate the growth of atherosclerotic plaques. This article proposes a biomaterials-based therapeutic intervention for depletion of non-regulated cholesterol accumulation and inhibition of inflammation of macrophages. Macromolecules with high scavenger receptor (SR)-binding activity were investigated for SR-mediated delivery of agonists to cholesterol-trafficking nuclear liver-X receptors. From a diverse feature space of a family of amphiphilic macromolecules of linear and aromatic mucic acid backbones modified with varied aliphatic chains and conjugated with differentially branched poly(ethylene glycol), a key molecule (carboxyl-terminated, C12derivatized, linear mucic acid backbone) was selected for its ability to preferentially bind scavenger receptor A (SR-A) as the key target. At a basal level, this macromolecule suppressed the pro-inflammatory signaling of activated THP-1 macrophages while competitively lowering oxLDL uptake in vitro through scavenger receptor SRA-1 targeting. To further deplete intracellular cholesterol, the core macromolecule structure was exploited to solubilize a hydrophobic small molecule agonist for nuclear Liver-X Receptors, which regulate the efflux of intracellular cholesterol. The macromolecule-encapsulated agonist system was found to reduce oxLDL accumulation by 88% in vitro in comparison to controls. In vivo studies were designed to release the macromolecules (with or without encapsulated agonist) to injured carotid arteries within Sprague Dawley rats fed a high fat diet, conditions that yield enhanced cholesterol accumulation and macrophage recruitment. The macromolecules lowered intimal levels of accumulated cholesterol (50% for macromolecule alone; 70% for macromolecule-encapsulated agonist) and inhibited macrophage retention (92% for macromolecule; 96% for macromoleculeencapsulated agonist; 4 days) relative to non-treated controls. Thus, this study highlights the promise of designing bioactive macromolecule therapeutics based on scavenger receptor targeting, for potential management of vascular arterial disease.

Research paper thumbnail of Core crosslinkable polymeric micelles from PEG?lipid amphiphiles as drug carriers

Journal of Materials Chemistry, 2004

Core crosslinkable micelles were prepared based on PEG–lipid amphiphiles. The branched hydrophobi... more Core crosslinkable micelles were prepared based on PEG–lipid amphiphiles. The branched hydrophobic domain was prepared by acylation of 2, 2-bis (hydroxymethyl) propionic acid (DMPA) with 10-undecenoyl chloride and pyridine as catalyst. Monohydroxyl poly ( ...

Research paper thumbnail of Nanoscale Amphiphilic Starlike Macromolecules with Carboxy, Methoxy and Amine-terminated Chain Ends

Journal of Bioactive and Compatible Polymers, 2006

Amphiphilic star-like macromolecules (ASMs) with chain ends terminating as methoxy-, carboxy and ... more Amphiphilic star-like macromolecules (ASMs) with chain ends terminating as methoxy-, carboxy and amine groups were synthesized for use as drug solubilization and delivery systems. Hydrophobic mucic acid derivatives were conjugated to the pentaerythritol tetraacrylate as the core molecule, then poly(ethylene glycol) chains with specific functionalized chain ends were attached. With respect to size in solution, the ASMs with longer alkyl

Research paper thumbnail of Comparison of PEG chain length and density on amphiphilic macromolecular nanocarriers: Self-assembled and unimolecular micelles

Two classes of amphiphilic macromolecules were evaluated for drug delivery applications: those th... more Two classes of amphiphilic macromolecules were evaluated for drug delivery applications: those that exist as unimolecular micelles and those that self-assemble in aqueous solution to form micelles. This study compares the poly(ethylene glycol) (PEG) chain length and density that constitute the corona of both classes. In particular, the effect of PEG branching on micellar size, water-solubility, resolubilization rate, drug loading efficiency and drug release rate were analyzed. Pluronic P85 and Cremophor EL, commonly used in pharmaceutical applications, were used as controls. Indomethacin (IMC) was used as the drug for encapsulation, release and resolubilization experiments. Results indicated that smaller micellar sizes, higher water solubilities and faster resolubilization rates were achieved from higher PEG densities compared to linear PEG analog of similar mass. Further, micellar sizes of both higher density PEG and linear PEG macromolecules were constant over a wide temperature range (2-70°C). In contrast, Cremophor EL formed aggregates at 15°C and Pluronic P85 underwent a size transition at 45°C. IMC loading efficiencies for all amphiphilic macromolecules were comparable to controls. However, faster resolubilization and slower drug release were observed for higher density PEG macromolecules compared to linear PEG analogs and controls.

Research paper thumbnail of Comparison of PEG chain length and density on amphiphilic macromolecular nanocarriers: Self-assembled and unimolecular micelles

Acta Biomaterialia, 2009

Two classes of amphiphilic macromolecules were evaluated for drug delivery applications: those th... more Two classes of amphiphilic macromolecules were evaluated for drug delivery applications: those that exist as unimolecular micelles and those that self-assemble in aqueous solution to form micelles. This study compares the poly(ethylene glycol) (PEG) chain length and density that constitute the corona of both classes. In particular, the effect of PEG branching on micellar size, water-solubility, resolubilization rate, drug loading efficiency and drug release rate were analyzed. Pluronic P85 and Cremophor EL, commonly used in pharmaceutical applications, were used as controls. Indomethacin (IMC) was used as the drug for encapsulation, release and resolubilization experiments. Results indicated that smaller micellar sizes, higher water solubilities and faster resolubilization rates were achieved from higher PEG densities compared to linear PEG analog of similar mass. Further, micellar sizes of both higher density PEG and linear PEG macromolecules were constant over a wide temperature range (2-70 degrees C). In contrast, Cremophor EL formed aggregates at 15 degrees C and Pluronic P85 underwent a size transition at 45 degrees C. IMC loading efficiencies for all amphiphilic macromolecules were comparable to controls. However, faster resolubilization and slower drug release were observed for higher density PEG macromolecules compared to linear PEG analogs and controls.

Research paper thumbnail of Engineered Polymeric Nanoparticles for Receptor-Targeted Blockage of Oxidized Low Density Lipoprotein Uptake and Atherogenesis in Macrophages

Biomacromolecules, 2006

Strategies to prevent the uptake of modified low density lipoproteins (LDLs) by immune cells, a m... more Strategies to prevent the uptake of modified low density lipoproteins (LDLs) by immune cells, a major trigger of inflammation and atherogenesis, are challenged by complex interfacial factors governing LDL receptor-mediated uptake. We examine a new approach based on a family of "nanoblockers", which are designed to examine the role of size, charge presentation, and architecture on inhibition of highly oxidized LDL (hoxLDL) uptake in macrophages. The nanoblockers are macromolecules containing mucic acid, lauryl chloride, and poly(ethylene glycol) that self-assemble into 15-20 nm nanoparticles. We report that the micellar configuration of the macromolecules and the combined display of anionic (carboxylate) groups in the hydrophobic region of the nanoblockers caused the most effective inhibition in the uptake of hoxLDL by IC21 macrophages. The nanoblockers primarily targeted SR-A and CD36, the major scavenger receptors and modulated the "atherogenic" phenotype of cells in terms of the degree of cytokine secretion, accumulation of cholesterol, and "foam cell" formation. These studies highlight the promise of synthetically engineered nanoblockers against oxidized LDL uptake.

Research paper thumbnail of Amphiphilic Scorpion-like Macromolecules as Micellar Nanocarriers

Journal of Bioactive and Compatible Polymers, 2008

... DOI: 10.1177/0883911508097498 2008 23: 532 Journal of Bioactive and Compatible Polymers Jelen... more ... DOI: 10.1177/0883911508097498 2008 23: 532 Journal of Bioactive and Compatible Polymers Jelena Djordjevic, Leilani S. Del Rosario, Jinzhong Wang and Kathryn E. Uhrich Amphiphilic Scorpion-like Macromolecules as Micellar Nanocarriers Published by: ...

Research paper thumbnail of Local Polarity and Microviscosity in the Hydrophobic Cores of Amphiphilic Starlike and Scorpion-like Macromolecules

Macromolecules, 2007

... Karen E. Steege, Jinzhong Wang, Kathryn E. Uhrich,* and Edward W. Castner, Jr.*. Department o... more ... Karen E. Steege, Jinzhong Wang, Kathryn E. Uhrich,* and Edward W. Castner, Jr.*. Department of Chemistry and Chemical Biology Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey 08854-8087. ...

Research paper thumbnail of Dual use of amphiphilic macromolecules as cholesterol efflux triggers and inhibitors of macrophage athero-inflammation

Biomaterials, 2011

Activated vascular wall macrophages can rapidly internalize modified lipoproteins and escalate th... more Activated vascular wall macrophages can rapidly internalize modified lipoproteins and escalate the growth of atherosclerotic plaques. This article proposes a biomaterials-based therapeutic intervention for depletion of non-regulated cholesterol accumulation and inhibition of inflammation of macrophages. Macromolecules with high scavenger receptor (SR)-binding activity were investigated for SR-mediated delivery of agonists to cholesterol-trafficking nuclear liver-X receptors. From a diverse feature space of a family of amphiphilic macromolecules of linear and aromatic mucic acid backbones modified with varied aliphatic chains and conjugated with differentially branched poly(ethylene glycol), a key molecule (carboxyl-terminated, C12derivatized, linear mucic acid backbone) was selected for its ability to preferentially bind scavenger receptor A (SR-A) as the key target. At a basal level, this macromolecule suppressed the pro-inflammatory signaling of activated THP-1 macrophages while competitively lowering oxLDL uptake in vitro through scavenger receptor SRA-1 targeting. To further deplete intracellular cholesterol, the core macromolecule structure was exploited to solubilize a hydrophobic small molecule agonist for nuclear Liver-X Receptors, which regulate the efflux of intracellular cholesterol. The macromolecule-encapsulated agonist system was found to reduce oxLDL accumulation by 88% in vitro in comparison to controls. In vivo studies were designed to release the macromolecules (with or without encapsulated agonist) to injured carotid arteries within Sprague Dawley rats fed a high fat diet, conditions that yield enhanced cholesterol accumulation and macrophage recruitment. The macromolecules lowered intimal levels of accumulated cholesterol (50% for macromolecule alone; 70% for macromolecule-encapsulated agonist) and inhibited macrophage retention (92% for macromolecule; 96% for macromoleculeencapsulated agonist; 4 days) relative to non-treated controls. Thus, this study highlights the promise of designing bioactive macromolecule therapeutics based on scavenger receptor targeting, for potential management of vascular arterial disease.

Research paper thumbnail of Core crosslinkable polymeric micelles from PEG?lipid amphiphiles as drug carriers

Journal of Materials Chemistry, 2004

Core crosslinkable micelles were prepared based on PEG–lipid amphiphiles. The branched hydrophobi... more Core crosslinkable micelles were prepared based on PEG–lipid amphiphiles. The branched hydrophobic domain was prepared by acylation of 2, 2-bis (hydroxymethyl) propionic acid (DMPA) with 10-undecenoyl chloride and pyridine as catalyst. Monohydroxyl poly ( ...

Research paper thumbnail of Nanoscale Amphiphilic Starlike Macromolecules with Carboxy, Methoxy and Amine-terminated Chain Ends

Journal of Bioactive and Compatible Polymers, 2006

Amphiphilic star-like macromolecules (ASMs) with chain ends terminating as methoxy-, carboxy and ... more Amphiphilic star-like macromolecules (ASMs) with chain ends terminating as methoxy-, carboxy and amine groups were synthesized for use as drug solubilization and delivery systems. Hydrophobic mucic acid derivatives were conjugated to the pentaerythritol tetraacrylate as the core molecule, then poly(ethylene glycol) chains with specific functionalized chain ends were attached. With respect to size in solution, the ASMs with longer alkyl

Research paper thumbnail of Comparison of PEG chain length and density on amphiphilic macromolecular nanocarriers: Self-assembled and unimolecular micelles

Two classes of amphiphilic macromolecules were evaluated for drug delivery applications: those th... more Two classes of amphiphilic macromolecules were evaluated for drug delivery applications: those that exist as unimolecular micelles and those that self-assemble in aqueous solution to form micelles. This study compares the poly(ethylene glycol) (PEG) chain length and density that constitute the corona of both classes. In particular, the effect of PEG branching on micellar size, water-solubility, resolubilization rate, drug loading efficiency and drug release rate were analyzed. Pluronic P85 and Cremophor EL, commonly used in pharmaceutical applications, were used as controls. Indomethacin (IMC) was used as the drug for encapsulation, release and resolubilization experiments. Results indicated that smaller micellar sizes, higher water solubilities and faster resolubilization rates were achieved from higher PEG densities compared to linear PEG analog of similar mass. Further, micellar sizes of both higher density PEG and linear PEG macromolecules were constant over a wide temperature range (2-70°C). In contrast, Cremophor EL formed aggregates at 15°C and Pluronic P85 underwent a size transition at 45°C. IMC loading efficiencies for all amphiphilic macromolecules were comparable to controls. However, faster resolubilization and slower drug release were observed for higher density PEG macromolecules compared to linear PEG analogs and controls.