Samuel Agro

Student: Samuel Agro

Project: Synthesis of Hybrid Outer Membrane Vesicles for Drug Delivery through Cell Membranes

View: Research Poster (PDF)

Institution: Lehigh University

Major: Chemical and Biomolecular Engineering

Advisor: Angela Brown

Abstract

Development of resistance to antibiotics of some of the most common forms of bacteria has cost the United States $21-34 billion per year with an estimated additional 8 million days in the hospital [1]. Finding a solution to this problem is difficult, because the development of new therapeutics has slowed in recent years, and current antibiotics are overprescribed and misused. Therefore, we seek novel methods of delivery for existing drugs to sites of bacterial infection.

Outer membrane vesicles (OMVs) from Gram-negative bacteria are important carriers of endotoxins, genetic material, and other virulence factors. It has been shown that delivery of antibiotics to Pseudomonas aeruginosa cells via OMVs is as effective in reducing colony count and growth as treatment by free antibiotics [2], but the fact that OMVs are unstable at body temperature and replete with cellular artifacts makes them an imperfect vehicle for drug delivery. To overcome this issue, we have developed an approach to create liposome-OMVs (L-OMVs) by extruding OMVs from a hypervesiculating strain of Escherichia coli K12 with liposomes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Our results show that the antibiotic-laden L-OMVs are stable at body temperature over many days, and that the L-OMVs do not aggregate or disintegrate over the same time frame. Future experiments will monitor the delivery of antibiotics to the pathogenic P. aeruginosa cells using fluorescent dye. We expect that L-OMVs could improve the delivery and efficacy of antibiotics, providing a well-needed tool in the fight against resistance.

[1] U.S. Department of Health and Human Services, CDC. (2019).
[2] Kadurugamuwa, J. L. & Beveridge, T. J. J. Bacteriol. (1996).