Porous Silica Nanoparticles for Targeted and Controlled Release of Biomolecules

Amirali Popat (2012). Porous Silica Nanoparticles for Targeted and Controlled Release of Biomolecules PhD Thesis, Aust Institute for Bioengineering & Nanotechnology, The University of Queensland.

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Author Amirali Popat
Thesis Title Porous Silica Nanoparticles for Targeted and Controlled Release of Biomolecules
School, Centre or Institute Aust Institute for Bioengineering & Nanotechnology
Institution The University of Queensland
Publication date 2012-03
Thesis type PhD Thesis
Total pages 93
Total colour pages 25
Total black and white pages 68
Language eng
Subjects 100708 Nanomaterials
100709 Nanomedicine
100703 Nanobiotechnology
Abstract/Summary Nanomaterials technology can serve as a non-invasive and biocompatible platform for the delivery of a broad range of therapeutics, and has many applications in the veterinarian and other primary industries. The creation of smart, stimuli-responsive systems that respond to subtle changes in the local cellular environment is likely to yield long-term solutions to many of the current delivery problems. One such example is the effective targeted delivery and controlled release of biocides such as imidacloprid, and fipronil. In Australia, the timber industry is worth an estimated $10 billion per year. Termites pose a great problem to the industry, causing up to $2 billion damage to the housing industry alone. The project aims to develop micro/nano encapsulation technology for targeted delivery and controlled release of biomolecules using mesoporous silica nanoparticles (MSNs) as the carriers. In developing the biocide-delivery system to target the entire termite colony, the system will increase the efficiency of delivery and reduce the amount of biocide released into the environment. These novel coated particles, with the encapsulated biocides, will be gathered as food by termites at aggregation stations and carried back to the colony. Once ingested, the biocide will be orally transferred to nest-mates and after a controlled delay, released inside the body of the termites. Herein we report for the first time agricultural biocide loaded into porous structure of silica nanoparticles. To achieve further controlled delivery, ethyl cellulose coated MSNs were successfully synthesised using novel S/W/O/W emulsion technology. The controlled delay is expected to allow the biocide to be distributed throughout the colony before release. Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), X-Ray Diffraction (XRD), and Fourier Transform Infra-red spectrometry (FTIR) were used to characterise the particles. Biocide release from ethyl cellulose coated composite particles showed slower sustained release than uncoated particles. Finally, these composite microparticles were tested in a lab scale in-vivo study where release of both imidacloprid and fipronil was tested against termites and mortality rates were compared between pure biocides, nanoparticles formulations and microparticles. We believe that this novel method can be applied to a wide variety of inorganic nanoparticles to achieve controlled release. Moreover, these particles are utilised for loading and controlled release of biological molecules such as drugs, genes, DNA etc. We have developed pH and enzyme responsive drug delivery systems based on MSNs. Chitosan was used to develop highly efficient pH responsive nanoparticulate system based on phosphoramidate chemistry. Construction of efficient chitosan coating relies on covalent bonding between phosphonate groups on the surface of the mesoporous silica nanoparticles (MSNs) and amino groups on chitosan using phosphoramidate bonding. To evaluate the efficiency of this controlled release system, ibuprofen was loaded onto MSNs and its release was evaluated over different pH conditions. In comparison with uncoated particles, coated particles showed sustained release over 48 hours proving the pH responsiveness of the system. Further, we developed MSNs based enzyme responsive drug delivery system using 3D cubic MCM-48 nanoparticles. MCM-48 nanoparticles were first functionalised by iodopropyl group to achieve high reactivity towards nucleophiles. Sulfasalazine a pro-drug of sulfapyridine and 5-amino salicylic acid was attached to the above mentioned group via nucleophilic substitution reaction to form highly stable azo-reductase responsive nanoparticulate system. We proved that this system only responds to azo-redctase present inside colon with zero release in absence of enzyme, irrespective of the pH of the solution. Through its multi-perspective approach, this thesis has demonstrated the promises of the developed novel mesoporous silica nanoparticles in advancing agricultural and biomedical applications.
Controlled release
stimuli responsive
Enzyme responsive
pH responsive
Additional Notes 17,23,25,27,28,30,38,41,47,51,54,60,67,75-88 This page numbers are of pdf page numbers.

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Created: Wed, 27 Jun 2012, 16:23:20 EST by Amirali Popat on behalf of Library - Information Access Service