Text

theses

The appearance of resistant strains of bacteria in community healthcare facilities is a common occurrence with growing severity. Cases of resistance to β-lactam drugs such as Methicillin have been shown in Staphylococcus aureus (MRSA) and Staphylococcus epidermis (MRSE), among many others, and these resistances limit therapeutic options. The synthetic glycopeptide antibiotic Vancomycin is considered one of the last lines of defense for these types of resistant infections. Failures in antibiotic therapy at this stage come from inadequate drug concentration at the infected sites, reduction of activity due to local acidity, and toxicity associated with accumulation in non-infected tissue. To solve these issues, an environmentally-responsive lipid-based nanoparticle, or liposome, has been developed to deliver Vancomycin to local infection sites. These liposomes retain their drug contents at physiologic pH, increasing antibiotic circulation time. Additionally, they are selectively triggered to release their drug contents by the external stimulus of decreased pH of local infection sites. Encapsulation of Vancomycin in these liposomes was performed, showing stable retention and release between pH 7.4 and 5.5, respectively. Additionally, demonstration of the enhanced antibiotic activity of the pH-triggered nanoparticles was carried out through Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) studies. From the results, there is promising data suggesting that targeted delivery of Vancomycin using environmentally sensitive liposomes is a candidate for sustained and targeted antibiotic therapy in resistant bacterial infections.

ETD_6979

M.S.

Includes bibliographical references

by Timothy Holleran

doi:10.7282/T32809NQ

ETD graduate

The author owns the copyright to this work.