The immunological effects of intradermal particle-based vaccine delivery using a novel microinjection needle studied in a human skin explant model.

For intradermal (ID) immunisation, novel needle-based delivery systems have been proposed as a better alternative to the Mantoux method. However, the penetration depth of needles in the human skin and its effect on immune cells residing in the different layers of the skin has not been analyzed. A novel and user-friendly silicon microinjection needle (Bella-muTM) has been developed, which allows for a perpendicular injection due to its short needle length (1.4-1.8 mm) and ultrashort bevel. We aimed to characterize the performance of this microinjection needle in the context of the delivery of a particle-based outer membrane vesicle (OMV) vaccine using an ex vivo human skin explant model. We compared the needles of 1.4 and 1.8 mm with the conventional Mantoux method to investigate the depth of vaccine injection and the capacity of the skin antigen-presenting cell (APC) to phagocytose the OMVs. The 1.4 mm needle deposited the antigen closer to the epidermis than the 1.8 mm needle or the Mantoux method. Consequently, activation of epidermal Langerhans cells was significantly higher as determined by dendrite shortening. We found that five different subsets of dermal APCs are able to phagocytose the OMV vaccine, irrespective of the device or injection method. ID delivery using the 1.4 mm needle of a OMV-based vaccine allowed epidermal and dermal APC targeting, with superior activation of Langerhans cells. This study indicates that the use of a microinjection needle improves the delivery of vaccines in the human skin.

In vivo performance testing of the novel Medspray wet aerosol inhaler.

BACKGROUND: Monodisperse salbutamol inhalers were compared to select the optimal mass median aerodynamic diameter: 4.0, 5.0 or 6.0 microm. METHODS: Fifteen mild asthmatic patients participated. In all a FEV(1)-response of >12% (vs. baseline) or >200 mL after inhalation of 200 microg salbutamol was measured. Each patient was studied four times with intervals of 1 week (three active and one placebo inhaler). First, 10 microg salbutamol was administered, followed by 10, 20, and 40 microg, resulting in cumulative doses of 10, 20, 40, and 80 microg salbutamol. The FEV(1) and other lung function parameters were assessed at baseline and 30 min after inhalation of each consecutive dose. Five minutes later a next inhalation was given. RESULTS: The 4.0- and 5.0-microm droplets did not differ from placebo (p = 0.502, p = 0.127), but the 6.0-microm droplets differed significantly (p = 0.003). The difference between 6.0-4.0 microm droplets was significant (p = 0.020), but not between the 6.0-5.0 microm droplets (p = 0.129). The FEV(1) increase after 80-microg salbutamol for the 6.0-microm droplets was 243 +/- 144 mL. CONCLUSIONS: The study showed that the 6.0-microm droplets differed from the others in terms of FEV(1)-improvement, and hence, are the most efficacious of the three evaluated.

In vitro performance testing of the novel Medspray wet aerosol inhaler based on the principle of Rayleigh break-up.

PURPOSE: A new inhaler (Medspray) for pulmonary drug delivery based on the principle of Rayleigh break-up has been tested with three different spray nozzles (1.5; 2.0 and 2.5 mum) using aqueous 0.1% (w/w) salbutamol and 0.9% (w/w) sodium chloride solutions. MATERIALS AND METHODS: Particle size distributions in the aerosol were measured with the principles of time of flight (APS) and laser diffraction (LDA). RESULTS: The Medspray inhaler exhibits a highly constant droplet size distribution in the aerosol during dose emission. Droplets on the basis of Rayleigh break-up theory are monodisperse, but due to some coalescence the aerosols from the Medspray inhaler are slightly polydisperse. Mass median aerodynamic diameters at 60 l.min(-1) from APS are 1.42; 1.32 and 1.27 times the theoretical droplet diameters (TD's) and median laser diffraction diameters are 1.29; 1.14 and 1.05 times TD for 1.5; 2.0 and 2.5 mum nozzles (TD: 2.84; 3.78 and 4.73 mum respectively). CONCLUSIONS: The narrow particle size distribution in the aerosol from the Medspray is highly reproducible for the range of flow rates from 30 to 60 l.min(-1). The mass median aerodynamic droplet diameter can be well controlled within the size range from 4 to 6 mum at 60 l.min(-1).