Project Details
Description
Project Summary
Engineered Polymer Nanoemulsions for Treatment of Wound Biofilm Infections
The goal of the proposed research to create new therapeutics targeting multidrug-resistant biofilm infections.
These infections are difficult to treat. The refractory nature of biofilm infections make them non-responsive to
standard antibiotics, a situation exacerbated by acquired antibacterial resistance.
In our research, we have integrated the nanomedicine capabilities of Rotello with wound biofilm expertise of
Patel to develop crosslinked nanoemulsions (XNEs) that use a crosslinked polymer network to stabilize
nanodroplets of essential oils. These XNEs kill biofilm-based bacteria with minimal effects on host cells and can
eradicate biofilms through incorporation of antimicrobials into the oil component of the XNE. XNEs have good
efficacy (killing ≥99% of bacteria in biofilms) using the in vivo wound biofilm model developed by Patel. Consistent
with other antimicrobial nanomaterials, however, killing is less effective in vivo than in vitro.
In our proposed research, Rotello will develop new block copolymers to generate block copolymer XNE (B-XNE)
therapeutics. The B-XNEs will then be incorporated into hydrogel wound dressings to provide controlled release
of B-XNEs to treat wound infections. B-XNEs and B-XNEs in wound dressings will be tested in vitro and in vivo
using realistic and challenging wound biofilm models.
Aim 1: Rotello will synthesize block copolymers and use these to parametrically vary size and charge of B-XNEs.
These B-XNEs will then be used to carry antibiotics, providing synergistic activity with essential oils. B-XNEs will
be screened for activity using luminescent methicillin-resistant Staphylococcus aureus (MRSA) biofilms, and
then tested against other bacterial species by Rotello and Patel. Co-culture models employing mammalian cells
will be used to downselect agents that maximize antibacterial activity and minimize mammalian cell toxicity.
Aim 2: Rotello will incorporate B-XNEs into hydrogels to provide antimicrobial wound dressings. B-XNEs and
hydrogels will be co-engineered to provide controlled release of B-XNEs. These B-XNE will be screened using
luminescent MRSA to identify promising B-XNE-hydrogel combinations, and further tested as in Aim 1 by Rotello
and Patel.
Aim 3: Rotello and Patel will use murine wound biofilm models to test B-XNEs and B-XNE wound dressings.
These studies will combine parametric pilot experiments using luminescent MRSA by Rotello with full pre-clinical
evaluation by Patel with MRSA and Acinetobacter baumannii wound biofilms. Efficacy in these models will be
quantified by decreased bacterial counts, enhanced wound healing, and diminished purulence as outcomes.
Status | Active |
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Effective start/end date | 7/24/18 → 6/30/24 |
Funding
- National Institute of Allergy and Infectious Diseases: $377,967.00
- National Institute of Allergy and Infectious Diseases: $393,246.00
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