Effect of Controlled Ice Nucleation on Stability of Lactate Dehydrogenase During Freeze-Drying

Fang, Ruiming; Tanaka, Kazunari; Mudhivarthi, Vamsi K.; Bogner, Robin H.; Pikal, Michael J.

doi:10.1016/j.xphs.2017.10.020

Cited by 35 publications

(21 citation statements)

References 24 publications

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“…These results are in line with the work by Vollrath et al, 29 where the application of controlled nucleation did not significantly affect the stability of 2 IgG1 antibodies. Our findings compare fairly well also with the report by Fang et al, 28 where a controlled nucleation approach was found to improve LDH stability after freeze-thawing. However, Fang et al also observed that the controlled nucleation technique was not equally beneficial for LDH stability during drying.…”

Section: Discussionsupporting

confidence: 92%

“…47 More specifically, the protein mobility responsible for both unfolding and aggregation in the dried state is significantly enhanced in the presence of water. The absence of beneficial effects on LDH post-drying stability observed by Fang et al 28 may therefore be at least partially explained by the higher water content during drying in the case of controlled nucleation.…”

Section: Discussionmentioning

confidence: 89%

“…Geidobler et al 26 evidenced that controlled ice nucleation may be applied to reduce reconstitution time of highly concentrated lyophilized protein product, and it was reported that it also helped to suppress glass fogging, that is, the undesired migration of protein solutions up on the inner walls of glass vials during the freezing step of lyophilization. 27 Moreover, Fang et al 28 studied the effect of controlled nucleation on the stability of lactate dehydrogenase (LDH) during both freezing and freeze-drying, but their results were not conclusive. In fact, they found that controlled nucleation remarkably improved LDH recovery after freeze-thawing and also increased batch homogeneity.…”

Section: Introductionmentioning

confidence: 99%

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Vacuum-Induced Surface Freezing for the Freeze-Drying of the Human Growth Hormone: How Does Nucleation Control Affect Protein Stability?

Oddone

Arsiccio

Duru

et al. 2020

Journal of Pharmaceutical Sciences

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In the present work, the effect of controlled nucleation on the stability of human growth hormone (hGH) during freeze-drying has been investigated. More specifically, the vacuum-induced surface freezing technique has been compared to conventional freezing, both with and without an annealing step. Size exclusion chromatography and cell-based potency assays have been used to characterize the formation of soluble aggregates and the biological activity of hGH, respectively. The results obtained indicate that controlled nucleation has a positive effect on both cycle performance and product homogeneity because of the formation of bigger ice crystals, and characterized by a narrower dimensional distribution. From the point of view of hGH stability, we observed that vacuum-induced surface freezing is not detrimental to the biological activity of the protein, or aggregate formation. In addition, the effect of 2 different formulations, including trehalose or cellobiose, on protein preservation was also considered for this study.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Vacuum-Induced Surface Freezing for the Freeze-Drying of the Human Growth Hormone: How Does Nucleation Control Affect Protein Stability?

Oddone

Arsiccio

Duru

et al. 2020

Journal of Pharmaceutical Sciences

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“…The peak at 280 nm was monitored, and an extinction coefficient of 1.44 mL/(mg cm) was used for calculations. 26 Three different formulations were prepared: A) 5% w/w sucrose, B) 5% w/w trehalose, and C) 2.5% w/w sucrose þ2.5% w/w trehalose. All the formulations were prepared in 5 mM potassium phosphate buffer.…”

Section: Methodsmentioning

confidence: 99%

“…1), sensitive to stresses encountered during the freeze-drying process. [17][18][19][20][21][22][23][24][25][26] The ability of excipients to preserve LDH during freezing, or in the dried state, will be first investigated using MD, with reference to the previously cited mechanisms of preferential exclusion, water replacement, and vitrification. The results obtained for LDH will be shown to be in line with those for hGH presented in our previous works, showing that the analysis performed is not protein specific but should rather be generally applicable.…”

Section: Introductionmentioning

confidence: 99%

Designing the Optimal Formulation for Biopharmaceuticals: A New Approach Combining Molecular Dynamics and Experiments

Arsiccio

Paladini

Pattarino

et al. 2019

Journal of Pharmaceutical Sciences

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Rapidly freeze‐dried human red blood cells for pre‐transfusion alloantibody testing reagents

Alves

Garnier

2021

J Biomed Mater Res

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Prior to transfusion of red blood cells (RBCs), recipients must be tested for the presence of alloantibodies to avoid immune complications. Liquid‐preserved reagent RBCs with known blood group antigen phenotypes are used for testing. However, these reagents have practical constraints, including limited shelf‐life and require constant refrigeration. To address these issues, we explore the effects of rapid freeze‐drying conditions with trehalose cryoprotectant (0.1–1 M concentrations) on human RBCs and storage of freeze‐dried RBCs (FDRBCs) at room temperature (RT) for up to 12 months. We report that rapid freeze‐drying of RBCs for 2.5 hr with 0.5 M trehalose achieves recoverable cells with near‐normal morphological shape, although size‐reduced. The FDRBCs are metabolically active and functional in antibody‐agglutination tests by the column agglutination test (CAT) for ABO and Rhesus‐D blood group antigens. Expression of the Duffy blood group protein (CD234) decreases by 50% after freeze‐drying RBCs. The initial recovery rate is ≤25%; however, 43% of these FDRBCs are still recoverable after RT storage for 12 months. In this proof‐of‐principle study, we show that rapid freeze‐drying can stabilize RBCs. Further refinements to improve the recovery rate and preservation of antigenic epitopes will make FDRBCs a practical alternative source of reagent RBCs for pre‐transfusion alloantibody identification.

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Effect of Controlled Ice Nucleation on Stability of Lactate Dehydrogenase During Freeze-Drying

Cited by 35 publications

References 24 publications

Vacuum-Induced Surface Freezing for the Freeze-Drying of the Human Growth Hormone: How Does Nucleation Control Affect Protein Stability?

Vacuum-Induced Surface Freezing for the Freeze-Drying of the Human Growth Hormone: How Does Nucleation Control Affect Protein Stability?

Designing the Optimal Formulation for Biopharmaceuticals: A New Approach Combining Molecular Dynamics and Experiments

Rapidly freeze‐dried human red blood cells for pre‐transfusion alloantibody testing reagents

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