The development of stable influenza vaccine powder formulations for new needle - free dosage forms

Influenza virosomes are reconstituted influenza virus envelopes that may be used as vaccines or as carrier systems for cellular delivery of therapeutic molecules. Here we present a procedure to generate influenza virosomes as a stable dry-powder formulation by freeze-drying (lyophilization) using an amorphous inulin matrix as a stabilizer. In the presence of inulin the structural integrity and fusogenic activity of virosomes were fully preserved during freeze-drying. For example, the immunological properties of the virosomes, i.e. the HA potency in vitro and the immunogenic potential in vivo, were maintained during lyophilization in the presence of inulin. In addition, compared to virosomes dispersed in buffer, inulin-formulated virosomes showed substantially prolonged preservation of the HA potency upon storage. Also the capacity of virosomes to mediate cellular delivery of macromolecules was maintained during lyophilization in the presence of inulin and upon subsequent storage. Specifically, when dispersed in buffer, virosomes with encapsulated plasmid DNA lost their transfection activity completely within 6 weeks, whereas their transfection activity was fully preserved for at least 12 weeks after incorporation in an inulin matrix. Thus, in the presence of inulin as a stabilizing agent, the shelf-life of influenza virosomes with and without encapsulated macromolecules was considerably prolonged. Formulation of influenza virosomes as a dry-powder is advantageous for storage and transport and offers the possibility to develop needle-free dosage forms e.g. for oral, nasal, pulmonal, or dermal delivery.