Development and Testing of a Spray-Dried Tuberculosis Vaccine Candidate in a Mouse Model.

Converting a vaccine into a thermostable dry powder is advantageous as it reduces the resource burden linked with the cold chain and provides flexibility in dosage and administration through different routes. Such a dry powder presentation may be especially useful in the development of a vaccine towards the respiratory infectious disease tuberculosis (TB). This study assesses the immunogenicity and protective efficacy of spray-dried ID93+GLA-SE, a promising TB vaccine candidate, against in a murine model when administered via different routes.

Formulation strategies for bacteriophages to target intracellular bacterial pathogens.

Bacteriophages (Phages) are antibacterial viruses that are unaffected by antibiotic drug resistance. Many Phase I and Phase II phage therapy clinical trials have shown acceptable safety profiles. However, none of the completed trials could yield data supporting the promising observations noted in the experimental phage therapy.

Trileucine as a dispersibility enhancer of spray-dried inhalable microparticles.

The formation of trileucine-containing spray-dried microparticles intended for pulmonary delivery was studied in depth. A single-particle method was employed to study the shell formation characteristics of trileucine in the presence of trehalose as a glass former, and an empirical correlation was proposed to predict the instance of shell formation. A droplet chain instrument was used to produce and collect monodisperse particles to examine morphology and calculate particle density for different levels of trileucine.

Microparticle encapsulation of a tuberculosis subunit vaccine candidate containing a nanoemulsion adjuvant via spray drying.

Spray drying is a technique that can be used to stabilize biopharmaceuticals, such as vaccines, within dry particles. Compared to liquid pharmaceutical products, dry powder has the potential to reduce costs associated with refrigerated storage and transportation. In this study, spray drying was investigated for processing an adjuvanted tuberculosis subunit vaccine, formulated as an oil-in-water nanoemulsion, into a dry powder composed of microparticles.

Development of a formulation platform for a spray-dried, inhalable tuberculosis vaccine candidate.

Protection against primarily respiratory infectious diseases, such as tuberculosis (TB), can likely be enhanced through mucosal immunization induced by direct delivery of vaccines to the nose or lungs. A thermostable inhalable dry powder vaccine offers further advantages, such as independence from the cold chain. In this study, we investigate the formulation for a stable, inhalable dry powder version of ID93 + GLA-SE, an adjuvanted subunit TB vaccine candidate, containing recombinant fusion protein ID93 and glucopyranosyl lipid A (GLA) in a squalene emulsion (SE) as an adjuvant system, via spray drying.

Development of a Lyophilization Process for Bacteriophage Storage and Transport.

Bacteriophages are a sustainable alternative to control pathogenic bacteria in the post-antibiotic era. Despite promising reports, there are still obstacles to phage use, notably titer stability and transport-associated expenses for applications in food and agriculture. In this study, we have developed a lyophilization approach to maintain phage titers, ensure efficacy and reduce transport costs of bacteriophages.

Trileucine and Pullulan Improve Anti-Campylobacter Bacteriophage Stability in Engineered Spray-Dried Microparticles.

Spray drying biologics into a powder can increase thermal stability and shelf-life relative to liquid formulations, potentially eliminating the need for cold chain infrastructure for distribution in developing countries. In this study, process modelling, microparticle engineering, and a supplemented phase diagram were used to design physically stable fully amorphous spray-dried powder capable of stabilizing biological material. A greater proportion of anti-Campylobacter bacteriophage CP30A remained biologically active after spray drying using excipient formulations containing trehalose and a high glass transition temperature amorphous shell former, either trileucine or pullulan, as compared to the commonly used crystalline shell former, leucine, or a low glass transition temperature amorphous shell former, pluronic F-68.

Prophylaxis of H37Rv Infection in a Preclinical Mouse Model via Inhalation of Nebulized Bacteriophage D29.

Globally, more people die annually from tuberculosis than from any other single infectious agent. Unfortunately, there is no commercially-available vaccine that is sufficiently effective at preventing acquisition of pulmonary tuberculosis in adults. In this study, pre-exposure prophylactic pulmonary delivery of active aerosolized anti-tuberculosis bacteriophage D29 was evaluated as an option for protection against infection.

Spray-dried anti-Campylobacter bacteriophage CP30A powder suitable for global distribution without cold chain infrastructure.

Campylobacter jejuni is a leading cause of foodborne illness globally. In this study, a spray drying and packaging process was developed to produce a thermally-stable dry powder containing bacteriophages that retains biological activity against C. jejuni after long distance shipping at ambient temperature.

Amorphous pullulan trehalose microparticle platform for respiratory delivery.

Spray drying biologics and small-molecule drugs can increase their thermal stability relative to liquid dosage forms and allow for widespread distribution to developing countries without cold chain infrastructure. In this study, pullulan trehalose powder is spray dried for inhalation. The powder is characterized in terms of manufacturability, physical stability, device compatibility, and aerosol performance.

Atmospheric Spray Freeze Drying of Sugar Solution With Phage D29.

Therapeutic bacteriophages offer a potential alternative approach in the treatment of drug resistant bacteria. In the present study, we examine the ability of atmospheric spray freeze-drying (ASFD) to process bacteriophage D29 into a solid dry formulation. Bacteriophage D29 is of particular interest due to its ability to infect .

Jet nebulization of bacteriophages with different tail morphologies - Structural effects.

It was previously demonstrated that the loss of infectivity of a myovirus PEV44 after jet nebulization was closely related to a change in bacteriophage (phage) structure. In this follow-up study, we further examined the impact of jet nebulization on tailed phages, which constitute 96% of all known phages, from three different families, Podoviridae (PEV2), Myoviridae (PEV40) andSiphoviridae (D29). Transmission electron microscopy (TEM) identified major changes in phage structures after jet nebulization, correlating with their loss of infectivity.

Effect of storage temperature on the stability of spray dried bacteriophage powders.

This study aimed to assess the robustness of using a spray drying approach and formulation design in producing inhalable phage powders. Two types of Pseudomonas phages, PEV2 (Podovirus) and PEV40 (Myovirus) in two formulations containing different amounts of trehalose (70% and 60%) and leucine (30% and 40%) were studied. Most of the surface of the produced powders was found to be covered in crystalline leucine.

Anti-Tuberculosis Bacteriophage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler.

Purpose: To compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) D29 with three inhalation devices.

Methods: Phage D29 lysate was amplified to a titer of 11.8 ± 0.

Effects of storage conditions on the stability of spray dried, inhalable bacteriophage powders.

This study aimed to develop inhalable powders containing phages active against antibiotic-resistant Pseudomonas aeruginosa for pulmonary delivery. A Pseudomonas phage, PEV2, was spray dried into powder matrices comprising of trehalose (0-80%), mannitol (0-80%) and l-leucine (20%). The resulting powders were stored at various relative humidity (RH) conditions (0, 22 and 60% RH) at 4°C.

Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections.

Purpose: The potential of aerosol phage therapy for treating lung infections has been demonstrated in animal models and clinical studies. This work compared the performance of two dry powder formation techniques, spray freeze drying (SFD) and spray drying (SD), in producing inhalable phage powders.

Method: A Pseudomonas podoviridae phage, PEV2, was incorporated into multi-component formulation systems consisting of trehalose, mannitol and L-leucine (F1 = 60:20:20 and F2 = 40:40:20).

Use of Extrathoracic Deposition Models for Patient-Specific Dose Estimation during Inhaler Design.

The lung dose of inhaled pharmaceutical aerosol that an individual will receive from an inhaler can now be more accurately estimated in light of recent extrathoracic deposition modeling that has correlated characteristic airway dimensions with deposition. This paper first summarizes the current state of extrathoracic deposition models, including recent developments that have quantified the effects of aerosol electrostatics and inhaler mouthpiece diameter on deposition. A generalized equation for predicting extrathoracic deposition in different subjects is then developed and average characteristic airway dimensions representative of different age groups are indicated.

Simulation of muscle and adipose tissue deformation in the passive human pharynx.

Quantifying the contribution of passive mechanical deformation in the human pharynx to upper airway collapse is fundamental to understanding the competing biomechanical processes that maintain airway patency. This study uses finite element analysis to examine deformation in the passive human pharynx using an intricate 3D anatomical model based on computed tomography scan images. Linear elastic properties are assigned to bone, cartilage, ligament, tendon, and membrane structures based on a survey of values reported in the literature.

An Apparatus to Deliver Mannitol Powder for Bronchial Provocation in Children Under Six Years Old.

Background: Currently bronchial provocation testing (BPT) using mannitol powder cannot be performed in children under 6 years. A primary reason is it is challenging for children at this age to generate a consistent inspiratory effort to inhale mannitol efficiently from a dry powder inhaler. A prototype system, which does not require any inhalation training from the pediatric subject, is reported here.

Pediatric in vitro and in silico models of deposition via oral and nasal inhalation.

Respiratory tract deposition models provide a useful method for optimizing the design and administration of inhaled pharmaceutical aerosols, and can be useful for estimating exposure risks to inhaled particulate matter. As aerosol must first pass through the extrathoracic region prior to reaching the lungs, deposition in this region plays an important role in both cases. Compared to adults, much less extrathoracic deposition data are available with pediatric subjects.

Effect of facial material softness and applied force on face mask dead volume, face mask seal, and inhaled corticosteroid delivery through an idealized infant replica.

Background: During the aerosol delivery device design and optimization process, in vitro lung dose (LD) measurements are often performed using soft face models, which may provide a more clinically relevant representation of face mask dead volume (MDV) and face mask seal (FMS) than hard face models. However, a comparison of MDV, FMS, and LD for hard and soft face models is lacking.

Methods: Metal, silicone, and polyurethane represented hard, soft, and very soft facial materials, respectively.