The administration of vaccines is a huge success story in modern medicine. However, one of the major drawbacks of most vaccine formulations is the need for administration by injection. Needle-stick injuries and transmission of blood-borne diseases due to re-use of disposable needles are a major issue in particular in developing countries. In addition, many commercially available vaccines require cold-chain transport and carefully controlled storage conditions due to the instability of vaccine antigens.
Combating these limitations in vaccine formulation require expertise in pharmaceutical technology to develop of novel dry vaccine formulations that can be applied using alternative routes of administration.
The epidermis of human skin, composed of live keratinocytes and immune cells, is a sensitive immune organ and a practical site for vaccine delivery. In addition, the epidermis lacks nerve endings and blood vessels, which make this site of needle-free administration even more attractive. Due to the skin barrier function, especially the protection of the stratum corneum of the most superficial layer of epidermis, it is not easy to delivery drugs or vaccines into epidermis or dermis. Epidermal powder immunization (EPI) is one of the most promising needle-free methods for delivery of powdered vaccines into skin. The current devices (such as PowderJect ND device) for EPI require the use of a helium chamber, which increases the cost dramatically and handling difficulty of the device.
The aim of this project is to investigate a new administration route of dry vaccines via epidermal powder injection using a novel device without using helium. The work is mainly focused on 1) developing suitable skin models which can be utilised to determine penetration of particles or powders of vaccines delivered by epidermal powder injection and 2) creating an antigen-loaded delivery system which can be used for epidermal powder immunisation.
Gelatin-based films with different mechanical properties were prepared and validated for the evaluation of intradermal powder injection devices. The mechanical properties of gelatin based films can be tailored to simulate human skin with different mechanical properties (individual, age, sex, etc.). The stability of the gelatin films was also investigated under long-term storage. In addition, CLSM was used as a novel tool to determine the depths and sizes of fluorescently labeled particles in the gelatin model.
Nanoparticles-in-microparticles (nano-in-micro) systems containing nanoparticles and antigens have been developed for the purpose of epidermal powder immunization. Antigen-loaded nanoparticles were incorporated into sugar-based microparticles (20-30 μm) consisting of trehalose, mannitol and dextran (TMD) by spray-freeze-drying (SFD). Cationic mesoporous silica (MSNP-NH2) nanoparticles were used to load ovalbumin (OVA) and H1N1 hemagglutinin (HA). PLGA nanoparticles were prepared to encapsulate OVA or SIINFEKL (an OVA peptide). The nano-in-micro systems comprising antigen-loaded nanoparticles and TMD matrices are useful for epidermal powder immunisation.
