Synthesis and surface modification of iron oxide nanoparticles for drug delivery

Abstract

Iron oxide nanoparticles are widely researched for a variety of medical applications. Understanding the properties of such compounds is important for further development of nanoparticle-based drugs. Although iron oxide nanoparticles have been used in the healthcare industry already especially as magnetic resonance imaging catalysts, there is still much to be understood about their potential to assist the delivery of the anticancer and anti-bacterial agents. Similarly, Traditional Chinese Medicines have been used for thousands of years for a variety of ailments and conditions. The active constituents of some of these medicines have recently been identified, with extensive research conducted to investigate the mechanisms of these compounds against various diseases. This thesis represents an effort to offer an alternative to current medications in the form of nanoparticles and natural herbal extracts. It employs a systematic approach by synthesizing and surface modifying the compounds before assessing the compounds in vitro against sarcoma cell lines and Clostridia bacterial species. Subsequent studies were conducted to examine in-depth the size-efficacy relationship and drug-release profile. Finally, a large-scale poultry trial was conducted to evaluate the feasibility of a derived compound in controlling outbreak of relevant diseases. A study involving three sizes of iron oxide nanoparticles were surface modified and tested against sarcoma cell lines. Surface modification with polyethylene glycol and loading of doxorubicin was performed for further evaluation of performance. A smaller sized nanoparticle with PEG coating was found to be most effective in killing the sarcoma cell lines suggesting increased uptake. The free iron ions potentially cross the nuclear or mitochondrial membrane to produce highly reactive radicals to cause direct damage to DNA, proteins and lipid peroxidation. This study establishes iron oxide nanoparticles loaded with doxorubicin and surface coated with polyethylene glycol to be a potential candidate as an anticancer drug. In vivo experiments to analyze bioavailability and mechanism of action are necessary for future development. The active constituent of the herb Goldenseal was identified as Berberine in previous literature. The antimicrobial activity of Berberine was assessed against Clostridia bacterial species representative of current livestock concerns including Clostridium Perfringens and Clostridium Difficile. The compound was found to have inhibitory and bactericidal effects in both. A subsequent study to evaluate feasibility of Berberine as an additive in poultry to control Clostridium Perfringens induced disease was conducted, with results demonstrating significant decrease in mortality and illness. However, the birds were seen to have decreased feed and water intake compared to birds on a standard feed and water diet. The results indicate a good basis for subsequent trials involving microbiota analysis, residues, and toxicology and dose-response efficacy of the compound. This study hopes to be a resource and inspiration for development of alternatives to current medicines. In particular, these findings underline the untapped potential of herbal medicines and the need to undergo an extensive screening of identified herbal active constituents against diseases of concern. This will be crucial as the impact of antibiotic use becomes more pronounced in the future.