Graduation Year

2015

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Chemistry

Degree Granting Department

Chemistry

Major Professor

Dr. Jianfeng Cai, Ph.D.

Co-Major Professor

Kirpal Bisht, Ph.D.

Committee Member

Kirpal Bisht, Ph.D.

Committee Member

Edward Turos, Ph.D.

Committee Member

Chuanhai Cao, Ph.D.

Keywords

Amphiphilic, Antimicrobial Polymers, Drug Delivery, Micelle

Abstract

The emergence of antibiotic resistant bacteria has prompted the research into novel kinds of antibacterial small molecules and polymers. Nature has solved this issue with the use of cationic antimicrobial peptides, which act as nonspecific antibiotics against invading species. Herein, we have tried to mimic this general mechanism in a biocompatible and biodegradable polymer micelle based on the polymerization of naturally occurring amino acids lysine and phenylalanine linked to a PEG tether. This amphiphilic structure allows for the spontaneous collapse into stable nanoparticles in solution, which contains a hydrophilic outer layer and a hydrophobic core. Our polymers have shown activity against clinically relevant strains including Methicillin Resistant S. epidermidis, B. subtilis, K. pneumoniae, and P. aeruginosa.

To further the application of our biopolymers, we have used them as drug delivery vehicles as well. First, we have used an anionic analogue based on glutamic acid to encapsulate a super hydrophobic drug Tanshinone IIA, and use it against a hepatoma bearing mouse model. Second, we have used a cationic analogue to form a complex with miRNA-139 and use it against a hepatoma bearing mouse model as well. In both cases, our PEG poly(amino acids)s have shown promising efficacy in drastically reducing the tumor size compared to the control only. Taken together, our results show that our nanoparticles have the potential to be versatile biomaterials as antibacterials as well as drug delivery vehicles in vivo.

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