Crosslinked Nanosponges for the Topical Treatment of Wound Biofilms The goal of the proposed research is the creation of therapeutics against multidrug-resistant biofilm infections. These infections are very difficult to treat: The refractory nature of biofilm infections make them highly resistant to standard antibiotics, a situation exacerbated by the development of antibiotic-resistant bacteria. In our research we will synergistically integrate the nanomedicine capabilities of Rotello with biofilm expertise of Patel. In preliminary research Rotello has developed crosslinked nanosponges imbibed with essential oil antimicrobials that penetrate and kill biofilm-based bacteria with minimal effect on host cells. Patel has created effective wound biofilm models that allow efficient assessment of therapeutics. In our proposed research we will develop new nanosponge therapeutics and test them against biofilms in vitro, in co-culture with mammalian cells, and finally in vivo.
Aim 1 : Rotello will fabricate and characterize polymeric nanosponges and optimize their activity against multi-drug resistant biofilms including S. aureus (MRSA) biofilm models. These nanosponges will be tested against mammalian cells in co-culture models, with the goal of maximizing antibacterial efficacy and minimizing mammalian cell toxicity.
Aim 2 : Rotello will screen therapeutics including antibiotics, quorum sensing inhibitors, and siderophores to create Generation 2 combination antibacterial agents.
Aim 3 : Patel will perform dosing and pre-clinical mouse studies of the optimized Generation 1 and 2 formulations, determining wound healing activity. Rotello will screen for inflammation.

Public Health Relevance

Significance: This research is focused on the development of antimicrobials for the treatment of wound biofilms. This research will impact the rapidly emerging threat of multidrug resistant bacterial infections, providing an alternative to surgical methods currently in use.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI134770-02
Application #
9749891
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Xu, Zuoyu
Project Start
2018-07-24
Project End
2022-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Massachusetts Amherst
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
153926712
City
Hadley
State
MA
Country
United States
Zip Code
01035
Gupta, Akash; Mumtaz, Shazia; Li, Cheng-Hsuan et al. (2018) Combatting antibiotic-resistant bacteria using nanomaterials. Chem Soc Rev :
Zhu, Dong Yu; Landis, Ryan F; Li, Cheng-Hsuan et al. (2018) Dynamically crosslinked polymer nanocomposites to treat multidrug-resistant bacterial biofilms. Nanoscale 10:18651-18656