Development of polymeric nanoparticles for gene delivery applications

Zoqlam, Randa (2021) Development of polymeric nanoparticles for gene delivery applications. Doctoral thesis, University of East Anglia.

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Abstract

Recent years have witnessed growing attention toward synthesising polymeric nanoparticles for pharmaceutical and biomedical applications. Therefore, microfluidics was introduced in an effort to advance nanoparticles synthesis and scaling up. However, a profound understanding of the synthesis processing parameters impact on the nanoparticle’s properties is of utmost importance to ensure their successful application. Although various research efforts have demonstrated the capacity of microfluidics to fabricate polymeric nanoparticles, there remains a need for a consistent study to examine the difference between microfluidics and the conventional synthesis methods in terms of nanoparticles properties, limitations, and ease of synthesis.

Polymeric nanoparticles have been exploited for gene delivery applications due to their advantages. Therefore, several studies examined the use of polymeric nanoparticles for pDNA/miRNAs delivery to target the molecular mechanisms underlying disease development. Osteoarthritis is among these diseases with no effective treatments. Therefore, several studies have focused on explaining the molecular mechanisms underlying osteoarthritis development and the role of miRNAs to address the potential gene targets that could be targeted by miRNAs delivery. However, to the best of our knowledge, no prior studies have examined the use of polymeric NPs for targeting potential gene targets of osteoarthritis by miRNA delivery.

The work presented herein offers a comprehensive description and comparison of the different synthesis methods of polymeric nanoparticles, emphasising the advantages and limitations of each synthesis method. In addition, the synthesised nanoparticles were tested for their efficacy in gene delivery applications, including pDNA delivery, to examine the impact of the nanoparticle’s properties on their transfection efficiency and miRNA-140 for targeting the molecular mechanisms underpinning osteoarthritis. The work conducted herein resulted in fabricating novel polymeric NPs that can efficiently deliver miRNA-140 to the chondrocytes to restore homeostasis by regulating the expression of FZD6, ADAMTS5, and MMP 13, three of the well-identified potential gene targets in osteoarthritis.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Pharmacy
Depositing User:	Chris White
Date Deposited:	27 Apr 2022 10:22
Last Modified:	27 Apr 2022 10:22
URI:	https://ueaeprints.uea.ac.uk/id/eprint/84806
DOI:

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