Date of Award

8-4-2023

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical and Chemical Engineering

Advisor(s)

Juntao Luo

Second Advisor

Ian Hosein

Keywords

Antibiotics;Daptomycin;Drug Delivery;Nanopaticles;Telodendrimer

Subject Categories

Life Sciences | Pharmacology | Pharmacology, Toxicology and Environmental Health

Abstract

The immune system plays a crucial role in fighting pathogens, but infections can occur if the immune system is unable to overcome them, leading to severe damage and death. Antibiotics and drug delivery techniques have helped save countless lives and improve the quality of life for patients. Daptomycin (Dap) is a powerful antibiotic used to treat gram-positive bacterial infections. However, its hydrophobic nature limits its effectiveness, and it requires the presence of calcium ions (Ca2+) for activation. In this study, a series of telodendrimer (TD) nanoparticle delivery systems were synthesized to improve daptomycin delivery. The TD nanoparticle systems showed effective binding with daptomycin, forming Dap-TD nanoparticles. Further more, this binding behavior between daptomycin and Ca2+ was examined via fluorescence spectrum, and indicated that TD can protection daptomycin via encapsulation to achieve broader distribution in the circulation. Dap-TDs demonstrated superior antibacterial activity against staphylococcus and streptococcus strains, while showing weaker but acceptable inhibition against listeria. Cell uptake studies showed efficient membrane penetration of the Dap-TDs, and the cytotoxicity levels, hemolytic effect were low or acceptable for some nanoformulation. These findings highlight the potential of telodendrimers as an effective drug delivery system for daptomycin and their capability to bind with bacterial remnants after bacterial cell death. This knowledge contributes valuable insights for the development of enhanced therapeutic approaches against Gram-positive bacterial infections.

Available for download on Monday, August 04, 2025

Included in

Pharmacology Commons

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