Formulating liposomes for increased antimicrobial activity toward Staphylococcus epidermidis

Stoncius, Kate; Pimentel, Emily; Felkner, Mae; Wolfgang, Hannah

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Formulating liposomes for increased antimicrobial activity toward Staphylococcus epidermidis

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Staphylococcus epidermidis biofilms are a major cause of medical device-related infections that often result in the removal and replacement of the offending device. Bacterial biofilm infections are difficult to treat through traditional antibiotic therapies due to their antibiotic recalcitrance. Vancomycin is an antibiotic used to treat antibiotic resistant strains of bacteria; however, conventional treatment poses a challenge due to its nephrotoxicity. To address antibiotic recalcitrance in bacterial biofilm infections, liposomes were investigated as potential drug delivery vehicles to decrease the concentration of vancomycin necessary for treatment. Two formulations of empty liposomes based on Food and Drug Administration (FDA) approved liposome therapies, such as Doxil®, were formulated and characterized based on size, polydispersity index, and zeta potential. Vancomycin encapsulated liposomes were formed using both passive and active loading methods. Passive loading techniques relied on rehydration of the lipid film, while the active loading method utilized a transmembrane ammonium sulfate pH gradient to drive vancomycin influx. Efficacy of vancomycin loaded liposomes formed using the active and passive loading methods were assessed against planktonic S. epidermidis in preliminary dosing trials, compared to the minimum inhibitory concentration (MIC) of free vancomycin on planktonic S. epidermidis. The assessment of encapsulation efficiency and dosing tests for vancomycin encapsulated liposomes formed using the passive and active loading methods did not suggest successful encapsulation of vancomycin, necessitating further experimental trials to validate these results. The findings presented in this paper lay the groundwork for future studies aimed at refining both passive and active loading procedures. Furthermore, future investigations will extend to exploring additional quantification methods for encapsulation efficiency. Testing will encompass a full determination of the MIC of vancomycin-loaded liposomes on planktonic S. epidermidis for both formulations. Eventually, the study will progress to evaluating the efficacy of these formulations on S. epidermidis biofilms. This project aims to reduce the concentration of vancomycin required to effectively treat S. epidermidis biofilm infections, thus addressing a critical need in antimicrobial therapy.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

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