Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)


Industrial and Physical Pharmacy

Committee Chair

Yoon Yeo

Committee Member 1

Kinam Park

Committee Member 2

Mohamed N. Seleem

Committee Member 3

Elizabeth M. Topp


Infections by intracellular bacteria have been recognized for many years, but they are difficult to cure due to the poor intracellular penetration of most antibiotics. To overcome poor intracellular delivery of antibiotics, we developed two polymeric nanoparticle formulation (NPs) that efficiently encapsulate and deliver antibiotics to the target cells – the macrophages in the liver and spleen. The first formulation (PpZEV) was based on a blend of polymers with distinct functions: (i) poly(lactic-co-glycolic acid) (PLGA, P) serving as the main delivery platform, (ii) polyethylene glycol-PLGA conjugate (PEG-PLGA, p) to help maintain an appropriate level of polarity for timely release of vancomycin, (iii) Eudragit E100 (a copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate, E) to enhance vancomycin encapsulation, and (iv) a chitosan derivative called ZWC (Z) to trigger pH-sensitive drug release. PpZEV NPs were preferentially taken up by the macrophages due to its size (500-1000 nm) and facilitated vancomycin delivery to the intracellular pathogens. Accordingly, PpZEV NPs showed better antimicrobial activity than free vancomycin against intracellular MRSA both in vitro and in vivo. Additionally, we developed a novel particle engineering method for encapsulating hydrophilic antibiotics in polymeric tannic acid nanocapsules. The hydrophilic drugs are encapsulated via quasi-emulsion method modified from inversion emulsion polymerization, using glycerol as the continuous phase instead of organic solvents. The method is simple, low-cost and can achieve >10% drug loading (drug/NPs) in all tested antibiotics (RRIKA, polymyxin B and vancomycin) in NPs with a size of 200 – 600 nm, a particle size suitable for intracellular drug delivery to macrophages. These results indicates that both PpZEV and pTA NPs are promising carriers for intracellular delivery of antibiotics.