The Contribution of the Inherent Restricted Mobility of Glassy Sugar Matrices to the Overall Stability of Freeze-Dried Bacteria Determined by Low-Resolution Solid-State 1H-NMR

Immobilization of proteins and other biomolecules in saccharide matrices leads to a series of peculiar properties that are relevant from the point of view of both biochemistry and biophysics, and have important implications on related fields such as food industry, pharmaceutics, and medicine. In the last years, the properties of biomolecules embedded into glassy matrices and/or highly concentrated solutions of saccharides have been thoroughly investigated, at the molecular level, through in vivo, in vitro, and in silico studies. These systems show an outstanding ability to protect biostructures against stress conditions; various mechanisms appear to be at the basis of such bioprotection, that in the case of some sugars (in particular trehalose) is peculiarly effective.Here we review recent results obtained in our and other laboratories on ternary protein-sugar-water systems that have been typically studied in wide ranges of water content and temperature. Data from a large set of complementary experimental techniques provide a consistent description of structural, dynamical and functional properties of these systems, from atomistic to thermodynamic level.In the emerging picture, the stabilizing effect induced on the encapsulated systems might be attributed to a strong biomolecule-matrix coupling, mediated by extended hydrogen-bond networks, whose specific properties are determined by the saccharide composition and structure, and depend on water content.

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“…In this case, dextran was shown to be particularly effective in blocking the low-frequency, large-scale, motions [178].…”

Section: Meso-and Macroscopic Levelmentioning

confidence: 95%

Proteins in Saccharides Matrices and the Trehalose Peculiarity: Biochemical and Biophysical Properties

Cordone¹,

Cupane²,

Emanuele

et al. 2015

COC

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“…As water is removed from the bacterial suspension the protectants in this suspension will concentrate, favoring the glassy state over the rubbery state of the cells. In the glassy state, characterized by a high viscosity (> 10 14 Pa.s), diffusion-controlled processes and mobility are severely slowed down (Aschenbrenner et al, 2014;Bryant et al, 2007). Probiotic cells are thus embedded in a glassy matrix with enhanced chemical and physical stability.…”

Section: Protective Agentsmentioning

confidence: 99%

“…Probiotic cells are thus embedded in a glassy matrix with enhanced chemical and physical stability. The transition from the glassy state to the rubbery state occurs at the glass transition temperature which is characteristic for each sugar (Aschenbrenner et al, 2014(Aschenbrenner et al, , 2012Grasmeijer et al, 2013).…”

Section: Protective Agentsmentioning

confidence: 99%

“…The removal of water causes the cell to contract, reducing the cell volume and bringing the bilayers into close apposition. Thus the gel phase is favored over the fluid phase (Aschenbrenner et al, 2014;Garvey et al, 2013;Golovina et al, 2009;Grasmeijer et al, 2013). The sugars are preferentially partitioned away from the polar head groups, increasing the interfacial free energy and therefore promoting the lipid phases.…”

Section: Protective Agentsmentioning

confidence: 99%

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Drying techniques of probiotic bacteria as an important step towards the development of novel pharmabiotics

Broeckx

Vandenheuvel

Claes

et al. 2016

International Journal of Pharmaceutics

252

188

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The increasing knowledge about the human microbiome leads to the awareness of how important probiotics can be for our health. Although further substantiation is required, it appears that several pathologies could be treated or prevented by the administration of pharmaceutical formulations containing such live health-beneficial bacteria. These pharmabiotics need to provide their effects until the end of shelf life, which can be optimally achieved by drying them before further formulation. However, drying processes, including spray-, freeze-, vacuum- and fluidized bed drying, induce stress on probiotics, thus decreasing their viability. Several protection strategies can be envisaged to enhance their viability, including addition of protective agents, controlling the process parameters and prestressing the probiotics prior to drying. Moreover, probiotic viability needs to be maintained during long-term storage. Overall, lower storage temperature and low moisture content result in good survival rates. Attention should also be given to the rehydration conditions of the dried probiotics, as this can exert an important effect on their revival. By describing not only the characteristics, but also the viability results obtained by the most relevant drying techniques in the probiotic industry, we hope to facilitate the deliberate choice of drying process and protection strategy for specific probiotic and pharmabiotic applications.

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“… 68 In a glassy state, sugars exhibit high viscosity and as a result molecular mobility of protein is restricted. 69 The transition from this glassy state to the undesirable rubbery state occurs at the T g . Excipients with low T g tend to crystallize upon spray drying and absence of an amorphous matrix destabilizes the protein.…”

Section: Spray Drying Vaccinesmentioning

confidence: 99%

Developments in the formulation and delivery of spray dried vaccines

Kanojia

Have

Soema

et al. 2017

Human Vaccines & Immunotherapeutics

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Spray drying is a promising method for the stabilization of vaccines, which are usually formulated as liquids. Usually, vaccine stability is improved by spray drying in the presence of a range of excipients. Unlike freeze drying, there is no freezing step involved, thus the damage related to this step is avoided. The edge of spray drying resides in its ability for particles to be engineered to desired requirements, which can be used in various vaccine delivery methods and routes. Although several spray dried vaccines have shown encouraging preclinical results, the number of vaccines that have been tested in clinical trials is limited, indicating a relatively new area of vaccine stabilization and delivery. This article reviews the current status of spray dried vaccine formulations and delivery methods. In particular it discusses the impact of process stresses on vaccine integrity, the application of excipients in spray drying of vaccines, process and formulation optimization strategies based on Design of Experiment approaches as well as opportunities for future application of spray dried vaccine powders for vaccine delivery.

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The Contribution of the Inherent Restricted Mobility of Glassy Sugar Matrices to the Overall Stability of Freeze-Dried Bacteria Determined by Low-Resolution Solid-State 1H-NMR

Cited by 8 publications

References 53 publications

Proteins in Saccharides Matrices and the Trehalose Peculiarity: Biochemical and Biophysical Properties

Proteins in Saccharides Matrices and the Trehalose Peculiarity: Biochemical and Biophysical Properties

Drying techniques of probiotic bacteria as an important step towards the development of novel pharmabiotics

Developments in the formulation and delivery of spray dried vaccines

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