Rishi Sharma - Academia.edu (original) (raw)

Papers by Rishi Sharma

Journal of controlled release : official journal of the Controlled Release Society, Jan 5, 2018

Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome chall... more Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome challenges relating to the blood-brain barrier (BBB), brain tissue penetration, and the targeting of specific cells. Neuroinflammation mediated by activated microglia is a major hallmark of several neurological disorders, making these cells a desirable therapeutic target. Building on the promise of hydroxyl-terminated generation four polyamidoamine (PAMAM) dendrimers (D4-OH) for penetrating the injured BBB and targeting activated glia, we explored if conjugation of targeting ligands would enhance and modify brain and organ uptake. Since mannose receptors [cluster of differentiation (CD) 206] are typically over-expressed on injured microglia, we conjugated mannose to the surface of multifunctional D4-OH using highly efficient, atom-economical, and orthogonal Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry and evaluated the effect of mannose conjugation on the specific cell u...

Biomaterials, 2010

We report a nanocarrier based on A 2 B type miktoarm polymers (A ¼ polyethylene glycol (PEG); B ¼... more We report a nanocarrier based on A 2 B type miktoarm polymers (A ¼ polyethylene glycol (PEG); B ¼ polycaprolactone (PCL)) for nimodipine (NIM), a hydrophobic drug with very poor aqueous solubility that is commonly prescribed for the prevention and treatment of delayed ischemic neurological disorders. The A 2 B star polymers were constructed on a core with orthogonal functionalities that facilitated the performance of "click" chemistry followed by ring-opening polymerization. These star polymers assemble into spherical micelles into which NIM can be easily loaded by the co-solvent evaporation method. The micelles obtained from the star polymer PEG775 2 ePCL5800 showed NIM encapsulation efficiency of up to 78 wt% at a feed weight ratio of 5.0%. The loading efficiency of the micelles was dependent on the length of the PCL arm in the A 2 B miktoarm polymers. Aqueous solubility of NIM was increased by w200 fold via micellar encapsulation. The in vitro release of NIM from the micelles was found to occur at a much slower rate than from its solution. Lipopolysaccharide induced nitric oxide production in N9 microglia cells was reduced in the presence of micelle-encapsulated NIM, as well as in the presence of micelles alone. The treatment of microglia with micelle-encapsulated NIM reduced the release of TNF-a, a pro-inflammatory cytokine. These results suggest that NIM-loaded miktoarm micelles could be useful in the treatment of neuroinflammation.

Polymer Chemistry, 2015

A novel strategy is described for the rapid syntheses of polyhydroxylated dendrimers in which the... more A novel strategy is described for the rapid syntheses of polyhydroxylated dendrimers in which the layer by layer building blocks are different from one another. The resulting dendrimers showed no cytotoxicity.

Polym. Chem., 2014

We report herein a novel “onion peel strategy” for the divergent construction of glycodendrimers ... more We report herein a novel “onion peel strategy” for the divergent construction of glycodendrimers using different building blocks at each layer of the dendritic growth.

Macromolecules, 2011

Designing well-defined multifunctional nanocarriers, into which a combination of the desired drug... more Designing well-defined multifunctional nanocarriers, into which a combination of the desired drug, an imaging dye, and a solubilizing agent can be covalently introduced, continues to be a focus of current research in theranostics.(1-3) Dendrimers(4) constitute an intriguing ...

Journal of Biomedical Optics, 2011

In this paper, we present a dual-modality imaging system combining three-dimensional (3D) continu... more In this paper, we present a dual-modality imaging system combining three-dimensional (3D) continuouswave transillumination fluorescence tomography with 3D ultrasound (US) imaging. We validated the system with two phantoms, one containing fluorescent inclusions (Cy5.5) at different depths, and another varying-thickness semicylindrical phantom. Using raster scanning, the combined fluorescence/US system was used to collect the boundary fluorescent emission in the X-Y plane, as well as recovered the 3D surface and position of the inclusions from US signals. US images were segmented to provide soft priors for the fluorescence image reconstruction. Phantom results demonstrated that with priors derived from the US images, the fluorescent reconstruction quality was significantly improved. As further evaluation, we show pilot in vivo results using an Apo-E mouse to assess the feasibility and performance of this system in animal studies. Limitations and potential to be used in artherosclerosis studies are then discussed.

Ecological Modelling, 2005

We developed a model to capture the interaction of two factors (habitat and hatchery indicators) ... more We developed a model to capture the interaction of two factors (habitat and hatchery indicators) on salmon abundance, and provide a framework for evaluating alternative restoration actions for salmon in the northwestern United States, assuming specific ocean conditions and harvest rates. We modeled different hypothetical coho salmon population trajectories in Issaquah creek (King County, western Washington, USA) as a function of land-use change and hatchery supplementation. The model can be tailored to address individual problems, areas and questions.

Biomaterials, 2010

We report a nanocarrier based on A 2 B type miktoarm polymers (A ¼ polyethylene glycol (PEG); B ¼... more We report a nanocarrier based on A 2 B type miktoarm polymers (A ¼ polyethylene glycol (PEG); B ¼ polycaprolactone (PCL)) for nimodipine (NIM), a hydrophobic drug with very poor aqueous solubility that is commonly prescribed for the prevention and treatment of delayed ischemic neurological disorders. The A 2 B star polymers were constructed on a core with orthogonal functionalities that facilitated the performance of "click" chemistry followed by ring-opening polymerization. These star polymers assemble into spherical micelles into which NIM can be easily loaded by the co-solvent evaporation method. The micelles obtained from the star polymer PEG775 2 ePCL5800 showed NIM encapsulation efficiency of up to 78 wt% at a feed weight ratio of 5.0%. The loading efficiency of the micelles was dependent on the length of the PCL arm in the A 2 B miktoarm polymers. Aqueous solubility of NIM was increased by w200 fold via micellar encapsulation. The in vitro release of NIM from the micelles was found to occur at a much slower rate than from its solution. Lipopolysaccharide induced nitric oxide production in N9 microglia cells was reduced in the presence of micelle-encapsulated NIM, as well as in the presence of micelles alone. The treatment of microglia with micelle-encapsulated NIM reduced the release of TNF-a, a pro-inflammatory cytokine. These results suggest that NIM-loaded miktoarm micelles could be useful in the treatment of neuroinflammation.

Journal of controlled release : official journal of the Controlled Release Society, Jan 5, 2018

Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome chall... more Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome challenges relating to the blood-brain barrier (BBB), brain tissue penetration, and the targeting of specific cells. Neuroinflammation mediated by activated microglia is a major hallmark of several neurological disorders, making these cells a desirable therapeutic target. Building on the promise of hydroxyl-terminated generation four polyamidoamine (PAMAM) dendrimers (D4-OH) for penetrating the injured BBB and targeting activated glia, we explored if conjugation of targeting ligands would enhance and modify brain and organ uptake. Since mannose receptors [cluster of differentiation (CD) 206] are typically over-expressed on injured microglia, we conjugated mannose to the surface of multifunctional D4-OH using highly efficient, atom-economical, and orthogonal Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry and evaluated the effect of mannose conjugation on the specific cell u...

Biomaterials, 2010

We report a nanocarrier based on A 2 B type miktoarm polymers (A ¼ polyethylene glycol (PEG); B ¼... more We report a nanocarrier based on A 2 B type miktoarm polymers (A ¼ polyethylene glycol (PEG); B ¼ polycaprolactone (PCL)) for nimodipine (NIM), a hydrophobic drug with very poor aqueous solubility that is commonly prescribed for the prevention and treatment of delayed ischemic neurological disorders. The A 2 B star polymers were constructed on a core with orthogonal functionalities that facilitated the performance of "click" chemistry followed by ring-opening polymerization. These star polymers assemble into spherical micelles into which NIM can be easily loaded by the co-solvent evaporation method. The micelles obtained from the star polymer PEG775 2 ePCL5800 showed NIM encapsulation efficiency of up to 78 wt% at a feed weight ratio of 5.0%. The loading efficiency of the micelles was dependent on the length of the PCL arm in the A 2 B miktoarm polymers. Aqueous solubility of NIM was increased by w200 fold via micellar encapsulation. The in vitro release of NIM from the micelles was found to occur at a much slower rate than from its solution. Lipopolysaccharide induced nitric oxide production in N9 microglia cells was reduced in the presence of micelle-encapsulated NIM, as well as in the presence of micelles alone. The treatment of microglia with micelle-encapsulated NIM reduced the release of TNF-a, a pro-inflammatory cytokine. These results suggest that NIM-loaded miktoarm micelles could be useful in the treatment of neuroinflammation.

Polymer Chemistry, 2015

A novel strategy is described for the rapid syntheses of polyhydroxylated dendrimers in which the... more A novel strategy is described for the rapid syntheses of polyhydroxylated dendrimers in which the layer by layer building blocks are different from one another. The resulting dendrimers showed no cytotoxicity.

Polym. Chem., 2014

We report herein a novel “onion peel strategy” for the divergent construction of glycodendrimers ... more We report herein a novel “onion peel strategy” for the divergent construction of glycodendrimers using different building blocks at each layer of the dendritic growth.

Macromolecules, 2011

Designing well-defined multifunctional nanocarriers, into which a combination of the desired drug... more Designing well-defined multifunctional nanocarriers, into which a combination of the desired drug, an imaging dye, and a solubilizing agent can be covalently introduced, continues to be a focus of current research in theranostics.(1-3) Dendrimers(4) constitute an intriguing ...

Journal of Biomedical Optics, 2011

In this paper, we present a dual-modality imaging system combining three-dimensional (3D) continu... more In this paper, we present a dual-modality imaging system combining three-dimensional (3D) continuouswave transillumination fluorescence tomography with 3D ultrasound (US) imaging. We validated the system with two phantoms, one containing fluorescent inclusions (Cy5.5) at different depths, and another varying-thickness semicylindrical phantom. Using raster scanning, the combined fluorescence/US system was used to collect the boundary fluorescent emission in the X-Y plane, as well as recovered the 3D surface and position of the inclusions from US signals. US images were segmented to provide soft priors for the fluorescence image reconstruction. Phantom results demonstrated that with priors derived from the US images, the fluorescent reconstruction quality was significantly improved. As further evaluation, we show pilot in vivo results using an Apo-E mouse to assess the feasibility and performance of this system in animal studies. Limitations and potential to be used in artherosclerosis studies are then discussed.

Ecological Modelling, 2005

We developed a model to capture the interaction of two factors (habitat and hatchery indicators) ... more We developed a model to capture the interaction of two factors (habitat and hatchery indicators) on salmon abundance, and provide a framework for evaluating alternative restoration actions for salmon in the northwestern United States, assuming specific ocean conditions and harvest rates. We modeled different hypothetical coho salmon population trajectories in Issaquah creek (King County, western Washington, USA) as a function of land-use change and hatchery supplementation. The model can be tailored to address individual problems, areas and questions.

Biomaterials, 2010

We report a nanocarrier based on A 2 B type miktoarm polymers (A ¼ polyethylene glycol (PEG); B ¼... more We report a nanocarrier based on A 2 B type miktoarm polymers (A ¼ polyethylene glycol (PEG); B ¼ polycaprolactone (PCL)) for nimodipine (NIM), a hydrophobic drug with very poor aqueous solubility that is commonly prescribed for the prevention and treatment of delayed ischemic neurological disorders. The A 2 B star polymers were constructed on a core with orthogonal functionalities that facilitated the performance of "click" chemistry followed by ring-opening polymerization. These star polymers assemble into spherical micelles into which NIM can be easily loaded by the co-solvent evaporation method. The micelles obtained from the star polymer PEG775 2 ePCL5800 showed NIM encapsulation efficiency of up to 78 wt% at a feed weight ratio of 5.0%. The loading efficiency of the micelles was dependent on the length of the PCL arm in the A 2 B miktoarm polymers. Aqueous solubility of NIM was increased by w200 fold via micellar encapsulation. The in vitro release of NIM from the micelles was found to occur at a much slower rate than from its solution. Lipopolysaccharide induced nitric oxide production in N9 microglia cells was reduced in the presence of micelle-encapsulated NIM, as well as in the presence of micelles alone. The treatment of microglia with micelle-encapsulated NIM reduced the release of TNF-a, a pro-inflammatory cytokine. These results suggest that NIM-loaded miktoarm micelles could be useful in the treatment of neuroinflammation.