Devices and formulations for pulmonary vaccination

University of Groningen, Department of Pharmaceutical Technology and Biopharmacy , Antonius Deusinglaan 1, 9713 AV Groningen , The Netherlands .
Expert Opinion on Drug Delivery (Impact Factor: 4.84). 06/2013; 10(10). DOI: 10.1517/17425247.2013.810622
Source: PubMed


Pulmonary vaccination could be a promising alternative to vaccination by injection. Administration of a vaccine to the lungs does not require the use of needles, which reduces the number of trained healthcare workers needed, the risk of needle-stick injuries and needle waste. Besides a systemic immune response, pulmonary vaccination may also induce a mucosal immune response. Such a local response may increase the effectiveness of vaccination against airborne pathogens. Although this route of administration has been studied for decades, no pulmonary vaccine is commercially available yet, due to various challenges mostly intrinsic to pulmonary drug delivery and vaccine formulation.

Areas covered:
This review discusses the inhalation devices and formulation strategies that may be suitable for the pulmonary administration of vaccines. In addition, critical parameters are addressed, such as the target population, to help assessing whether pulmonary administration of a specific vaccine may be feasible and beneficial or not.

Expert opinion:
A combined approach of inhalation device and vaccine formulation development is essential. This should result in a system that can effectively be used by the target population and can be produced at low costs. Only then, this challenging administration route can be successfully applied to large-scale vaccination programs.

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Available from: Henderik Frijlink, Oct 27, 2014
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    • "Powder formulation can be interesting for these biopharmaceuticals because it increases their stability and thus, their shelf life compared to aqueous formulations [3]. In addition to improved stability, having the product as a powder is also advantageous for the administration, since in humans dry powder inhalers (DPIs) are preferred over nebulizers for these products [2] [4] [5]. When administering a powder by inhalation, the powder particles should preferably have an aerodynamic diameter of 1–5 lm in order to reach the lungs effectively [6]. "
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    ABSTRACT: To evaluate powder formulations for pulmonary administration in pre-clinic research, the powder should be administered to the lungs of small laboratory animals. To do so properly, a device is needed that generates particles small enough to reach deep into the lungs. In this study a newly developed aerosol generator was tested for pulmonary administration of powder to the lungs of mice and its performance was compared to the only currently available device, the Penn-Century insufflator. Results showed that both devices generated powder particles of approximately the same size distribution, but the fine particle fraction needed for deep lung administration was strongly improved when the aerosol generator was used. Imaging studies in mice showed that powder particles from the aerosol generator deposited into the deep lung, where powder from the Penn-Century insufflator did not reach further than the conducting airways. Furthermore, powder administered by using the aerosol generator was more homogenously distributed over the five individual lungs lobes than powder administrated by using the Penn-Century insufflator. Copyright © 2014. Published by Elsevier B.V.
    European Journal of Pharmaceutics and Biopharmaceutics 10/2014; 88(3). DOI:10.1016/j.ejpb.2014.10.011 · 3.38 Impact Factor
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    ABSTRACT: Carbon dioxide Assisted Nebulization with a Bubble Dryer((R)) (CAN-BD) processing allows particles to be made in the 3-5 mum size range, which is desirable for lung delivery, without destroying biological activity. In response to the Grand Challenge in Global Health Initiative #3, we have been developing an inhalable needle-free live-attenuated measles virus vaccine for use in developing countries. Measles was chosen because it is the number one vaccine preventable killer of children worldwide. Powders were processed by CAN-BD, where a solution containing excipients and live-attenuated measles virus in water was mixed intimately with supercritical or near superctitical carbon dioxide to form an emulsion. The emulsion was expanded to atmospheric pressure through a flow restrictor. The resulting plume was dried by heated nitrogen and the powders collected on a filter at the bottom of the drying chamber. Powders were analyzed using varying techniques including X-ray diffraction, scanning electron microscopy, Andersen cascade impaction, differential scanning calorimetery, Karl Fischer titration, and viral plaque assay. CAN-BD has been used to produce powders of live-attenuated measles virus vaccine with characteristics desirable for lung delivery. The powders retain viral activity through forming and drying the microparticles by CAN-BD, and have passed the WHO stability test for 1 week at 37 degrees C. The powders have an amorphous character and a glass transition temperature of around 60 degrees C. Lyophilization, the present standard commercial method of processing measles vaccine makes solids with a water content of less than 1%. By substituting myo-inositol for sorbitol and using the CAN-BD drying technique the water content can be lowered to 0.5%. The most successful formulations to date have been based conceptually on the current lyophilized formulation, but with modifications to the type and amounts of sugar. Of current interest are formulations containing myo-inositol, as they retain high viral activity and have low initial water content.
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    ABSTRACT: Using a procedure of emulsification-lyophilization (PEL), adjuvant lipid A-cochleates (LACs) were prepared as a carrier for model antigen bovine serum albumin (BSA). With phosphatidylserine and lipid A as emulsifiers dissolved in oil phase (O), sucrose and CaCl2 in the inner water phase (W1), and BSA, sucrose and PEG2000 in the outer water phase (W2), the W1/O/W2 emulsions were prepared and subsequently lyophilized to form a dry product which was stable enough to be stored at room temperature. Upon rehydration of the dry products, cochleates formed with a size of 800nm and antigen association rates of 38%. After vaccination of mice through oral mucosal (o.m.) administration, LACs showed no side effects but induced potent immune responses as evidenced by high levels of IgG in the sera and IgA in the salivary, intestinal and vaginal secretions of mice. In addition, high levels of IgG2a and IFN-γ in the sera or culture supernatants of splenocytes of the immunized mice were also detected. These results revealed that LACs induced a mixed Th1/Th2 response against the loaded antigens. Thus, the LACs prepared by PEL were able to induce both systemic and mucosal immune responses and may act as a potent cold-chain-free oral mucosal vaccine adjuvant delivery system (VADS).
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