Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/143322
Title: FUNCTIONAL AND BIODEGRADABLE MACROMOLECULAR THERAPEUTICS FOR ANTI-INFECTIVE APPLICATIONS
Authors: WANG YING
Keywords: infectious diseases, antimicrobial resistance, biofilm, antimicrobial peptides, cationic albumins, polymeric micelles
Issue Date: 17-May-2017
Citation: WANG YING (2017-05-17). FUNCTIONAL AND BIODEGRADABLE MACROMOLECULAR THERAPEUTICS FOR ANTI-INFECTIVE APPLICATIONS. ScholarBank@NUS Repository.
Abstract: For the effective control of infectious diseases, novel and multi-dimensional strategies are highly demanded to overcome the limitations of antimicrobial therapeutics, such as emergence of drug resistance and side effects. In this thesis, we explored different class of macromolecular therapeutics for anti-infective applications. We firstly developed cationic antimicrobial peptides by conjugating immunomodulatory pentapeptide thymopentin with six arginines. The modified peptides possess in anti-mycobacterial activity with membranolytic mechanism and negligible in vitro hemolytic activities. The retention of immunomodulatory activity of the modified peptides was studied by their ability to resemble the induction of tumor necrosis factor in RAW 264.7 cells by thymopentin. Secondly, we developed cationic serum albumins to tackle antimicrobial resistance and biofilm-related infections. The impact of charge density and PEGylation profile on antimicrobial activity and toxicity was systematically investigated. Both the susceptibility of albumin-based antimicrobials to drug resistance development and their anti-biofilm activities were evaluated. Lastly, we developed polymeric micelles for the delivery of amphotericin B using polycarbonate/PEG diblock copolymers, to reduce its non-specific toxicity without appreciable loss in anti-fungal activity. Functional groups were incorporated into the polymers in order to enhance the interactions between polymers and Amphotericin B, inhibit self-aggregation of the drug, and achieve controlled drug release.
URI: http://scholarbank.nus.edu.sg/handle/10635/143322
Appears in Collections:Ph.D Theses (Open)

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