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Macrophage-Targeted Nanocarriers for Localized Treatment of Chronic Inflammation in Diabetic Wounds
Summary Data Summary
Applicant Smith, Andrew
E-Mail Address smi@illinois.edu
Project Title Macrophage-Targeted Nanocarriers for Localized Treatment of Chronic Inflammation
in Diabetic Wounds
CBU ID 20AU4143
External SubContract ID 32307-80
Diabetic Complication Wound Healing
Funding Program Group Pilot & Feasibility [PF2020]
Abstract Impaired wound healing in diabetes is the leading cause of lower extremity
amputation in the United States, resulting in 50% mortality after 5 years.
Chronic, localized inflammation is believed to be a causative factor in slow
healing in diabetic wounds, and macrophage cells are implicated as primary
mediators. In normal wounds, macrophages shift over time from a phenotype that
is pro-inflammatory to phenotypes that promote tissue repair, whereas
inflammatory phenotypes persist in the diabetic state to inhibit angiogenesis,
granulation tissue formation, and wound contraction required for healing.
Systemically administered anti-inflammatory agents do not improve healing in the
clinic or in preclinical models and in fact further exacerbate healing
impairment, likely due to off-target effects in cells in which the drug targets
facilitate tissue repair. The scientific premise of this Pilot and Feasibility
proposal is that nanocarriers can reroute the delivery of pharmaceutical agents
selectively to inflammatory macrophages in wounds after local administration to
eliminate off-target effects. Preliminary data show that polysaccharide-based
nanocarriers can deliver cyclooxygenase 2 (COX2) inhibitors to potently diminish
inflammatory cytokine expression and expedite wound healing in diabetic mouse
models. Aim 1 of this proposal is to evaluate formulations that maximize the
efficiency of targeted delivery to inflammatory macrophages in wounds using
fluorescent and radioisotopically labeled nanocarriers, evaluated ex vivo by
flow cytometry and gamma well counting. Aim 2 is to evaluate the efficacy of
COX2 inhibitor formulations toward diabetic wound healing and evaluate
off-target effects. A fundamental outcome of this work will be an understanding
of nanomaterial transport in wounds and receptor-mediated mechanisms to target
macrophage subpopulations in wounds. The nanocarrier delivery agents are based
on FDA-approved materials already in broad use, which may expedite clinical
testing if preclinical evaluations are promising. This work will be undertaken
by an interdisciplinary team comprising bioengineers (Smith Lab) who focus on
nanomaterial-based drug delivery and imaging agents, and immunologists and
vascular biologists (Gallagher Lab) who focus on molecular and cellular
mechanisms of diabetic wound healing.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel Dr. Katherine Gallagher
Salary Total Costs 19763
Supply Total Costs 1000
Equipment Total Costs 0
Travel/Other Total Costs 42403
Direct Costs 63166
Indirect Costs Proposed 36834
Total Costs Proposed 100000
Total Costs Approved 100000
Start Date 11/1/2020
End Date 10/31/2021
IFO Name Gregory, Linda
IFO E-Mail Address SPA@illinois.edu
IACUC/IRB No. 19213
IACUC/IRB Institution University of Illinois at Urbana-Champaign
Entity ID No. 37-6000511
Report Request Date 10/31/2021
T1D NO
TypeCount
Invoices 7
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  20AU414332307-80University of Illinois at Urbana-Champaign9/12/2022$18,059.96$10,583.15$28,643.11$0.13View PDF
  View  20AU414332307-80University of Illinois at Urbana-Champaign8/28/2023$4,098.62$2,401.79$6,500.41$0.13View PDF
  View  20AU414332307-80University of Illinois at Urbana-Champaign3/9/2022$14,920.88$8,743.64$23,664.52$0.13View PDF
  View  20AU414332307-80University of Illinois at Urbana-Champaign2/9/2022$12,605.28$7,386.68$19,991.96$0.13View PDF
  View  20AU414332307-80University of Illinois at Urbana-Champaign11/15/2021$5,827.09$3,414.67$9,241.76$0.13View PDF
  View  20AU414332307-80University of Illinois at Urbana-Champaign10/11/2021$5,827.11$3,414.69$9,241.80$0.13View PDF
  View  20AU414332307-80University of Illinois at Urbana-Champaign1/13/2023$1,826.85$889.46$2,716.31$0.13View PDF


Reports
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