Declaration 2 Publications
1.7 Overview of dissertation
The research work performed is presented in this thesis in the publication format, according to University of Kwa-Zulu Natal, College of Health Sciences guidelines. It specifies the inclusion of a brief introductory chapter, published papers and a final chapter on the conclusions. A PhD study requires at least three first authored papers, two of which must be experimental.
CHAPTER 2. BOOK CHAPTER: This chapter is a first authored book chapter titled
“Amphiphilic Dendrimers for Drug Delivery” in ‘Handbook of Materials for Nanomedicine’ 2nd Edition, that has been accepted and is in press, to be published by the internationally acclaimed publisherPan Stanford Publishing Pte, Singapore 2018, with Professor Vladmir Torchillin as the book editor. This book chapter focuses on the medical applications of amphiphilic dendrimers, such as drug delivery in various diseases, including infectious diseases. The modification of dendrimers to acquire amphiphilicity that results in improved the toxicity profile, enhanced efficiency and solubility of the loaded drugs was also discussed. The book chapter also included the design of smart drug delivery systems, and translational potential of the resulting drug delivery systems which is part of the main objective this study which involves synthesis of amphiphilic dendrimer-based system, synthesis of advanced smart materials and enhancement of efficiency and solubility antibiotics using nanobased strategies.
CHAPTER 3. EXPERIMENTAL PAPER 1: This chapter addresses Aim 1, Objectives 1- 6 and is a first authored experimental article published in an ISI international journal:
Journal of Controlled Release (Impact Factor = 7.877). This article highlights the
synthesis of a novel block copolymer dendrimer star polymer hybrid, the in vitro toxicity evaluation, formulation of the ultra-small vesicles (V-3-mPEA) to deliver VCM, molecular dynamics simulation of the self-assembly of a novel block copolymer dendrimer star polymer hybrid, and characterization of its physical and antibacterial properties both in vitro and in vivo.
CHAPTER 4. EXPERIMENTAL PAPER 3: This chapter addresses Aim 3, Objectives 1 – 6 and is a first authored experimental article communicated to Advanced Healthcare Materials (Impact Factor 5.76.) an ISI international journal (manuscript ID advhealthmat-S-18-01827). This article highlights the synthesis of a novel fatty acid quaternary lipid, the in vitro toxicity evaluation, formulation of a liposome with “On and Off” pH switches (OA-QL liposome) for targeted delivery of VCM, molecular dynamics simulation of the “On and Off” mechanism of the switches and binding affinity of the lipid on a model bacterial membrane, and characterization of its physical and antibacterial properties both in vitro and in vivo of the drug loaded liposome.
CHAPTER 5. EXPERIMENTAL PAPER 2: This chapter addresses Aim .2, Objectives 1 - 3 and is a first authored experimental article published in the ISI international journal ACS Molecular Pharmaceutics (Impact Factor = 4.556). This article highlights the formulation development of a novel FA-NS, and the characterization of its physical properties, aqueous solubility enhancement, enhanced antibacterial activity against methicillin sensitive and resistant S. aureus both in vitro and in vivo, and MD simulations on the formation of a stable nanosuspension.
CHAPTER 6. CO-AUTHORED PAPERS: In addition to the first authored experimental papers in Chapters, 3, 4 and 5 focusing on the aims 1, 2 and 3 I have also been involved in other research projects within our group as a team member. As these projects also focused on the broad aim of novel nanobased strategies to effectively treat bacterial infections, these papers have been included in the thesis. This chapter therefore includes two co-authored experimental papers and one review article published in ISI international journals: International Journal of Pharmaceutics (Impact Factor = 3.902), Journal of Biomolecular Structure & Dynamics (Impact Factor = 3.107) and Journal of Drug Delivery Science and Technology (Impact Factor = 2.297).
CHAPTER 7. CONCLUSION: This chapter includes the overall conclusions from research findings in the study, provides information on potential significance of the findings and makes recommendations for future research work in the field of strategic solutions to combat bacterial resistance to antibiotics.
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CHAPTER 2, BOOK CHAPTER