Internal microstructure of spray dried particles affects viral vector activity in dry vaccines.

To maintain the activity of sensitive biologics during encapsulation by spray drying, a better understanding of deactivation pathways in dried particles is necessary. The effect of solid-air interfaces within dried particles on viral deactivation was examined with three binary excipient blends, mannitol/dextran (MD), xylitol/dextran (XD), and lactose/trehalose (LT). Particles encapsulating human serotype 5 adenovirus viral vector (AdHu5) were produced via both spray drying and acoustic levitation.

Dextran Mass Ratio Controls Particle Drying Dynamics in a Thermally Stable Dry Powder Vaccine for Pulmonary Delivery.

Purpose: Thermally stable, spray dried vaccines targeting respiratory diseases are promising candidates for pulmonary delivery, requiring careful excipient formulation to effectively encapsulate and protect labile biologics. This study investigates the impact of dextran mass ratio and molecular weight on activity retention, thermal stability and aerosol behaviour of a labile adenoviral vector (AdHu5) encapsulated within a spray dried mannitol-dextran blend.

Methods: Comparing formulations using 40 kDa or 500 kDa dextran at mass ratios of 1:3 and 3:1 mannitol to dextran, in vitro quantification of activity losses and powder flowability was used to assess suitability for inhalation.

Validation of a diffusion-based single droplet drying model for encapsulation of a viral-vectored vaccine using an acoustic levitator.

Development of thermally stable spray dried viral-vectored vaccine powders is dependent on the selection of a proper excipient or excipient blend for encapsulation, which can be a time and resource intensive process. In this work, a diffusion-based droplet drying model was developed to compute droplet drying time, size, and component distribution. The model predictions were validated using an acoustic levitator to dry droplets containing protein-coated or fluorescently labelled silica nanoparticles (as adenoviral vector analogues) and a range of excipient blends.

Effect of Shear Stresses on Adenovirus Activity and Aggregation during Atomization To Produce Thermally Stable Vaccines by Spray Drying.

Considering the substantive potential benefits of thermally stable dry powder vaccines to public health, causes for inactivation of their sensitive viral vectors during preparation require intensive study. The focus of this work was atomization of suspensions containing encapsulating excipients and a human type 5 adenovirus, involving a detailed investigation of shear stresses in the nozzle of a spray dryer. Samples were sprayed at 25 °C into falcon tubes and immediately evaluated for viral activity by in vitro testing, minimizing the confounding of thermal effects on the deactivation of the virus, although interfacial stresses could not be decoupled from shear stresses.

Acoustic levitation as a screening method for excipient selection in the development of dry powder vaccines.

Spray drying is emerging as a promising technique to produce thermally stable powder vaccines containing viral vectors. One of the most important factors in developing dry powder vaccines is the selection of the excipient carrier, however this process is time intensive, and uses large amounts of costly viral material. In this work, an acoustic levitator modified with a hot air delivery system was evaluated for its ability to mimic spray drying and acts as a screening method for excipient selection.