Doctor of Philosophy (PhD)
First Advisor's Name
Joong ho Moon
First Advisor's Committee Title
Second Advisor's Name
Second Advisor's Committee Title
Third Advisor's Name
Yukching Tse Dinh
Third Advisor's Committee Title
Fourth Advisor's Name
Fourth Advisor's Committee Title
Fifth Advisor's Name
Fifth Advisor's Committee Title
Antimicrobial, Polymer, Poly(guanylurea), Amidinourea, Resistance, Conjugated polymer, Gene delivery
Date of Defense
Drug-resistant pathogens are emerging rapidly and thwart the treatment of common bacterial infectious diseases that can lead to death. Many contagious diseases remain difficult to treat because of acquired drug resistance. Compared to small antibiotics, which interrupt the intracellular biochemical processes, antimicrobial polymers with relatively high molecular weights offer a promising strategy to overcome drug resistance by disrupting the physical integrity of the membrane. Because of the unique mechanism, bacteria need a much longer time to develop resistance.
A new class of antimicrobial polymer in which the positive charge and hydrophobic/hydrophilic units are linearly connected in the amidinourea backbone was designed, synthesized, and tested for various bacteria including methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the effects of hydrophobicity and polymer molecular weights on antimicrobial activity by measuring minimum inhibitory concentrations (MIC) and hemolytic activities (HC50). Amidinourea antimicrobial polymers exhibit a promising MIC90 value (13 μg/mL) with low HC50, resulting in high selectivity (HC50/MIC90) against MRSA.
Many bacteria have developed resistance against Ciprofloxacin. To overcome the antibiotic resistance associated with Ciprofloxacin, we hypothesized that a steady release of Ciprofloxacin at the bacteria membrane can overcome the drug resistance because the local drug concentration can be overwhelmingly high to suppress the drug efflux pump expressed on the membrane. A series of homo and di-block copolymers containing Ciprofloxacin, as the form of prodrugs, was synthesized using ring-opening metathesis polymerization (ROMP), and we evaluated their antimicrobial efficacy.While homo polymers only containing Ciprofloxacin were inactive against almost all bacteria tested, di-block copolymers containing Cipro and triphenylphosphine exhibited some antimicrobial activity against wild type M. smegmatis.
Modulation of chemical environments at the positively charged polymeric materials can significantly influence the biophysical properties required for efficient cellular interaction and subsequent entry. Using intrinsic fluorescent conjugated polymers (CPs), we have demonstrated that the modulated guanidine group with various hydrophilic or hydrophobic moieties dramatically changed their cellular behaviors. We prepared a series of modified guanidine-containing CPs and examined their cellular behaviors by using confocal microscopic imaging. Details of the modification chemistry and modification-dependent cellular behaviors and a knockdown of a target protein in primary cells were discussed.
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Ahmed, Md Salauddin, "Synthesis of Antimicrobial Polymers to Overcome Antimicrobial Resistance" (2017). FIU Electronic Theses and Dissertations. 3692.
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