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Principal Investigator: Nathan Claude Gianneschi
Organization: NORTHWESTERN UNIVERSITY AT CHICAGO
Fiscal Year: 2024
Award: $319,998
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
Project Summary
The Polymeric Materials Synthesis and Characterizations Core will formulate, synthesize, and characterize lead
candidates for the mitigation of mustards and provide support and chemical expertise to other cores and projects.
The Core will be co-directed by Drs. Nathan Gianneschi (Dept. of Chemistry) and Stephen Miller (Dept. of
Microbiology-Immunology). A tiered approach will be taken to select and optimize such candidates. Initially
properties that enhance the efficacy of the materials would be determined and physiochemical analysis on the
materials of interest would be probed. One such example is our ability to enrich materials for radical scavenging
at the chemical doping level. Other properties would include surface charge, porosity, binding capacity, and
solubility of materials. Depending on the material and application for the skin or eyes, the candidate material will
be formulated as a nanoparticle, or as a surface coating and the delivery could be optimized for its specific
application. That is, materials can be prepared for delivery via direct application as a liquid solution or cast into
a film or in the case of PLGA Immune Modifying Particles (PLGA-IMPs) for intravenous infusion. After initial in
vitro and in vivo studies, materials will be scaled-up for clinical trials, with many of the proposed systems already
known to be amenable to that kind of scale-up. The Polymeric Materials Synthesis and Characterizations Core
will be responsible for advancing the synthesis of materials such as polymers from small molecules, will make
chemical modifications to improve lead compounds/materials, and will synthesize components for the Lipid-
Based Self-Assembled Materials Synthesis and Characterization Core. The goals of this core are to develop
formulations and delivery platforms for lead candidates such as melanin, biodegradable polymeric PLGA IMPs
(which will be further modified by encapsulating anti-inflammatory cytokines (IL-10 and TGF-β) and compounds
(e.g. Vitamin D), and peptide-based delivery systems for the skin and eyes by modifying their physiochemical
properties and by characterizing materials for scale-up and clinical translation. For the Polymeric Materials
Synthesis and Characterizations Core we propose the following Aims: Aim 1: Utilizing melanin for the
remediation and adsorption of mustards; Aim 2: Protein-Like Polymers for treatment of mustard gas in the eye;
and Aim 3: Production and characterization of negatively-charged, biodegradable PLGA Immune-Modifying
Nanoparticles (PLGA-IMPs) for therapeutic treatment of chemical tissue injury.
Terms: <Adsorption><Amino Acids><Angiogenesis Antagonists><Angiogenesis Blockers><Angiogenesis Inhibitors><Angiogenetic Antagonists><Angiogenetic Inhibitors><Angiogenic Antagonists><Angiogenic Inhibitors><Angiogenic Peptides><Angiostatic Agents><Anti-Angiogenetic Agents><Anti-Angiogenic Agents><Anti-Angiogenic Drugs><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Antiangiogenesis Agents><Antiangiogenic Agents><Antiangiogenic Drugs><Assay><Binding><Bioassay><Biological Assay><Biopolymers><Bis(beta-chloroethyl) Sulfide><Blood monocyte><Body Tissues><Bone-Derived Transforming Growth Factor><CSIF><CSIF-10><Cell Body><Cell Culture Techniques><Cells><Charge><Chemical Injury><Chemicals><Chemistry><Chloramin><Chlorethazine><Chlormethine><Clinical><Clinical Trials><Collaborations><Cytokine Synthesis Inhibitory Factor><Dermal injury><Di-2-chloroethyl Sulfide><Dichlorodiethyl Sulfide><Disciform macular degeneration><Disciform senile macular retinal degeneration><Encapsulated><Exposure to><Exudative AMD><Exudative age-related macular degeneration><Eye><Eyeball><Film><Formulation><Free Radical Scavenging><Glycolates><Goals><HN-2><HN2><Human><IL-10><IL10><IL10A><IV Infusion><Immune><Immunes><Immunology><In Vitro><Inflammation><Inflammatory><Interleukin 10 Precursor><Interleukin-10><Intravenous infusion procedures><Laboratories><Lead><Lipids><Liquid substance><Macrophage><Marrow monocyte><Mechlorethamine><Melanins><Methylchlorethamine><Microbiology><Milk Growth Factor><Modeling><Modern Man><Modification><Molecular Interaction><Mustard><Mustard Gas><Mustine><Mφ><Nature><Neovascular AMD><Neovascular age-related macular degeneration><Neovascularization Inhibitors><Nitrogen Mustard><Pb element><Peptides><Platelet Transforming Growth Factor><Play><Polymers><Porosity><Position><Positioning Attribute><Preparation><Production><Property><Proteins><Redness><Retina><Role><Site><Skin><Skin injury><Solubility><Sulfur Mustard><Surface><System><TGF B><TGF-beta><TGF-β><TGFbeta><TGFβ><Technology><Testing><Therapeutic><Tissues><Transforming Growth Factor beta><Transforming Growth Factor-Beta Family Gene><Translating><UV irradiated><UV irradiation><Universities><VIT D><Validation><Vitamin D><Wet AMD><Work><Yellow Cross Liquid><Yperite><aminoacid><antiangiogenic><biocompatible polymer><biodegradable polymer><bioresorbable polymer><carboxylate><cell culture><cell cultures><chemical trauma><chloromethine><clinical translation><clinically translatable><cutaneous injury><cytokine><degradable polymer><direct application><epidermal injury><experiment><experimental research><experimental study><experiments><fluid><glycolic acid><heavy metal Pb><heavy metal lead><improved><in vivo><injuries to skin><injury to tissue><innovate><innovation><innovative><interest><intravenous infusion><keratinocyte><lead candidate><liquid><materials science><monocyte><monomer><nano particle><nano-sized particle><nanomaterials><nanoparticle><nanoparticle therapy><nanosized particle><novel><particle><peptide aminoacid sequence><peptide sequence><polymer><polymeric><preparations><protein aminoacid sequence><remediation><scale up><self assembly><skin burn><small molecule><social role><surface coating><technology platform><technology system><therapeutic nanoparticles><tissue injury><tool><ultra violet irradiation><ultraviolet irradiation><uptake><validations><wet form of AMD>