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

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. The 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. The 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. Silica 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

Drug-loaded liposome-capped mesoporous core-shell magnetic nanoparticles for cellular toxicity study

Liposome-capped core-shell mesoporous silica-coated superparamagnetic iron oxide nanoparticles called 'magnetic protocells' were prepared as novel nanocomposites and used for loading anticancer drug doxorubicin (DOX) for cellular toxicity study. Cytotoxicity of the magnetic protocells with or without DOX was tested in vitro on commercial MCF7 and U87 cell lines under alternating magnetic field MCF7 cell line treated with the DOX-loaded nanoparticles under alternating magnetic field exhibited nearly 20% lower survival rate..

Open-Gated pH Sensor Fabricated on an Undoped-AlGaN/GaN HEMT Structure

The sensing responses in aqueous solution of an open-gated pH sensor fabricated on an AlGaN/GaN high-electron-mobility-transistor (HEMT) structure are investigated. Under air-exposed ambient conditions, the open-gated undoped AlGaN/GaN HEMT only shows the presence of a linear current region. This seems to show that very low Fermi level pinning by surface states exists in the undoped AlGaN/GaN sample. In aqueous solution, typical current-voltage (I-V) characteristics with reasonably good gate controllability are observed, showing that the potential of the AlGaN surface at the open-gated area is effectively controlled via aqueous solution by the Ag/AgCl gate electrode. The open-gated undoped AlGaN/GaN HEMT structure is capable of distinguishing pH level in aqueous electrolytes and exhibits linear sensitivity, where high sensitivity of 1.9 mA/pH or 3.88 mA/mm/pH at drain-source voltage, VDS = 5 V is obtained. Due to the large leakage current where it increases with the negative gate voltage, Nernstian like sensitivity cannot be determined as commonly reported in the literature. This large leakage current may be caused by the technical factors rather than any characteristics of the devices. Surprisingly, although there are some imperfections in the device preparation and measurement, the fabricated devices work very well in distinguishing the pH levels. Suppression of current leakage by improving the device preparation is likely needed to improve the device performance. The fabricated device is expected to be suitable for pH sensing applications

Enzyme immobilised novel core–shell superparamagnetic nanocomposites for enantioselective formation of 4-(R)-hydroxycyclopent-2-en-1-(S)-acetate

Lipase immobilized novel high surface area core–shell superparamagnetic nanoparticles have been fabricated and used as efficient reusable catalysts for the selective production of pharmaceutically important chiral isomers from meso-cyclopent-2-en-1,4-diacetate

Hermally responsive lipid coated superparamagnetic nanoparticles for frequency triggered drug delivery

Herein we report a fabrication method of core-shell type silica coated superparamagnetic iron oxide nanoparticles (SPIONs) with thermally responsive lipids for controlled and targeted drug delivery using Alternative Current (AC) magnetic field for potential applications in cancer therapy. Core-shell SPIONs, loaded with anticancer drug, Doxorubicin (DOX) were coated with lipids such as dipalmitoylphosphatidylcholine (DPPC) and cholesterol so as to cap the mesopores. The particle size of the bare and coated SPIONs was measured using the dynamic light scattering technique, scanning and transmission electron microscopy (SEM and TEM). The change in surface morphology of bare and coated SPIONs was evidenced from SEM. The in vitro drug loading and release studies were carried in phosphate buffered saline (PBS) under the AC magnetic field as well as under thermal incubation condition at 37°C. The concentration of DOX in solution was determined by measuring the absorbance at 484 nm by UV-Visible spectrophotometer. The preliminary results indicate that the drug release behaviour under the AC magnetic field is relatively controlled compared to that of normal thermal incubation condition at 37°C