Chem Eng Master to PHD Transfer Seminar - Anushi Rajapaksa

Category: Seminar


14 December 2009
4pm - 5pm
Room 201, Building 69, Clayton campus Chem Eng - 4th Year Room

Production of Particulate vaccines and delivery of DNA vaccines driven by Surface Acoustic Wave Devices

The increase in the need for the effective delivery of potent vaccines requires a robust yet straightforward method for production of DNA-laden aerosols and biodegradable polymers. Aerosol delivery of drugs represents the next generation of vaccine delivery where the drug is deposited into the lung, providing a non-invasive route for the delivery of genetic therapeutics. The traditional methods attempted for the production of DNA aerosols include ultrasonic and jet nebulizers which fail to maintain the viability of large bio-molecules such as DNA due to the high shear rates induced during the atomization process. New and potent vaccines are of critical importance for existing (e.g. HIV, malaria, TB and cancer) and emerging diseases (e.g. pandemic influenza).

Presented is a novel system for the production of DNA aerosols and also biodegradable nanoparticles in a defined size range using surface acoustic wave (SAW) devices. The SAW technology provides a portable platform to achieve this goal where aerosol particles in the size range of 0.5-3.5 mm suitable for pulmonary delivery can be obtained while causing little damage to the integrity of the DNA molecules. SAWs are essentially acoustic waves with 10nm order amplitudes that originate as a result of the application of an alternating voltage onto an interdigital transducer patterned on a piezoelectric substrate. The leakage of acoustic radiation into a drop housing the DNA solution then results in its atomization to produce the micron dimension aerosols.

In the preliminary research, a solution containing a plasmid DNA (pDNA) vector encoding a 45 kDa P. yoelli merozoite surface protein 4/5(PyMSP4/5) as a potential malaria vaccine candidate was atomized using both 20 and 30MHz SAW devices. High levels of gene expression were observed in western blots from in-vitro experiments conducted using immortalized African green monkey kidney cells (COS-7) cells that were transfected with the post-atomized DNA.  Atomic Force Microscopy (AFM) images further confirmed the ability of this novel technique to preserve the integrity of DNA post-atomization for potential aerosol delivery. The low power consumption of the SAW atomization (1-3 W) together with its potential for miniaturization displays potential use of the SAW technology as a portable pulmonary delivery platform for gene delivery.

In addition to the development of effective therapeutic vaccines via aerosol delivery, the SAW technology can be used for the production of particulate vaccine carriers composed of biodegradable polymers. Most treatment or vaccination procedures require the antigen to migrate to the antigen-presenting cells in order to elicit sufficient immune responses. However, the antigen itself cannot reach the target site without the help of a carrier. Vaccine carrier systems composed of biocompatible and biodegradable compounds in the nanometer size range (2 – 100nm) have been shown to improve both cellular and immune responses. The particles obtained in the range of 40 – 90nm, where sizes were confirmed using dynamic light scattering measurements and scanning electron microcopy strongly convey the suitability of the SAW technology for enhanced antigen delivery.

Future stages of this research project will be devoted to engineering the size and composition of biodegradable nanoparticles produced via the SAW driven platform, to target to immune cells. A significant portion of the project will also be dedicated to testing the SAW driven nebulizer at delivering aerosolized vaccine formulations to the lungs of sheep, to prove an enhanced pulmonary and systemic immunity.

Enquiry:   Kate Malcolm | 53555