Study of porous magnetic nanocomposites for bio-catalysis and drug delivery (2016)

Despite advances in diagnostic procedures and treatments, the overall survival rate from cancer has not improved substantially over the past 30 years. One promising development is the encapsulation of toxic cancer chemotherapeutic reagents within biocompatible nanocomposite materials. The targeted stimuli triggered drug release restrict the toxic drugs to the tumour site, thereby reducing the effects of “free drug” on healthy tissues. One of the most versatile and safe materials used in medicine are iron oxide nanoparticles. This project describes the development of several formulations based on magnetite nanoparticles for drug delivery applications. Utilising magnetic nanoparticles in drug delivery systems allowed for the synergistic effects of hyperthermia and heat triggered drug released. The drug delivery systems developed in this project include magnetoliposomes, magnetic micelles, mesoporous silica-magnetite core-shell nanoparticles, liposome capped mesoporous silica-magnetite core-shell nanoparticles (protocells) and polymer capped mesoporous silica-magnetite core-shell nanoparticles. \nThe drug loading and release profiles of the developed nanomaterials were assessed using two different anticancer drugs; Mitomycin C (MMC) and Doxorubicin (DOX). The drug loading content and drug loading efficiency for different nanocomposites ranged from 0.48 to 10.30% and 16.16 to 85.85%, respectively. Drug release profiles were studied in vitro at 37°C at pH 5.5 and pH 7.4 and at hyperthermia elevated temperature of 43°C to evaluate the effects of pH and temperature on the release profiles. An AC magnetic field with frequency of 406 kHz and variable field of up to 200 G was used to induce magnetic heating and keep the temperature within hyperthermia treatment range. Compared to uncapped mesoporous silica nanoparticles capping the mesopores of the silica nanoparticles with liposome or polymer reduced the drug release by 52.7% and 41.5%, respectively.\nThe efficacy of doxorubicin-containing nanoparticles were evaluated in vitro against breast cancer and glioblastoma cell lines where different formulations demonstrated comparable or increased cytotoxicity compared to free drug. The cells treated with DOX loaded nanoparticles and hyperthermia demonstrated up to 89% lower viability compared to cells treated with free DOX.\nSilica coated magnetic nanoparticles were also used as enzymes (Pseudomonas Fluorescens Lipase (PFL) and Candida Rugosa Lipase (CRL)) supports in catalysis reactions. The enzymes were immobilised onto nanoparticles through physical adsorption and chemical bonding. The immobilised lipases were used in hydrolysis of pNPP and hydrolysis of cis-3,5-diacetoxy-1-cyclopentene to investigate the catalytic activity of the immobilized enzymes compared to free enzymes. The results indicated that free lipases provided slightly higher conversion than immobilised lipases in the first cycle however, the immobilised lipases were easily recycled and reused in sequential cycles which provides higher total yield per mg of lipase. The chemically immobilised lipase exhibited good reusability without loss of its activity in sequential cycles, however the physically adsorbed lipase showed reduced activity which could be explained by loss of enzyme during recycling between successive reactions. The CRL lipase activity were further assessed in the presence of an AC field where the results showed that exposure to the AC magnetic field resulted in increased lipase activity. The effect of reaction temperature on immobilised lipase activity were studied by performing the hydrolysis of cis-3,5-diacetoxy-1-cyclopentene at two temperatures of 25°C and 37°C where it was observed that both lipases exhibited higher activity at higher temperature which could be due to the fact that for PFL and CRL the optimum temperature is close to 37°C.