Stability of buffer-free freeze-dried formulations: A feasibility study of a monoclonal antibody at high protein concentrations

Garidel, Patrick; Pevestorf, Benjamin; Bahrenburg, Sven

doi:10.1016/j.ejpb.2015.09.017

Cited by 34 publications

(11 citation statements)

References 77 publications

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“…Upon evaluating buffer‐containing and buffer‐free silk foams, we confirmed that the lack of changes in the silk crystallinity upon water vapor exposure was due to the buffer, or salts within the buffer. Antibody buffers are typically formulation to stabilize the pH for long‐term antibody stability 55 . The presence of additional components such as Tween‐20 and L‐histidine have been shown to further stabilize antibodies and minimize protein aggregation 56,57 .…”

Section: Discussionmentioning

confidence: 99%

“…The presence of additional components such as Tween‐20 and L‐histidine have been shown to further stabilize antibodies and minimize protein aggregation 56,57 . However, studies have demonstrated that when antibodies are freeze‐dried for long term storage, these buffer components may not be necessary to retain stability 55 . Instead, inclusion of sugars such as sucrose or glycerol can provide stability through the lyophilization process 55,58 .…”

Section: Discussionmentioning

confidence: 99%

“…However, studies have demonstrated that when antibodies are freeze‐dried for long term storage, these buffer components may not be necessary to retain stability 55 . Instead, inclusion of sugars such as sucrose or glycerol can provide stability through the lyophilization process 55,58 . To tune antibody release from silk foams, additional work needs to be performed to remove buffer components while maintaining antibody stability and investigate the impact of varying the silk crystallinity on antibody release.…”

Section: Discussionmentioning

confidence: 99%

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Development of a dinutuximab delivery system using silk foams for GD2 targeted neuroblastoma cell death

Ornell

Chiu

Coburn

2020

J Biomedical Materials Res

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Neuroblastoma is the most common extracranial solid tumor of childhood and is associated with poor survival in high risk patients. Recently, dinutuximab (DNX) has emerged as an effective immunotherapy to treat patients with high risk neuroblastoma. DNX works through the induction of cell lysis via complement‐dependent cytotoxicity (CDC) or antibody dependent cellular cytotoxicity (ADCC). However, one third of patients who undergo DNX treatment exhibit tumor relapse and the therapy is dose limited by side effects such as severe pain. To overcome delivery challenges of DNX, including large size and dose limiting side effects, we fabricated a delivery system capable of sustained local delivery of bioactive DNX utilizing silk fibroin. We evaluated the impact of silk properties (MW, crystallinity, and concentration) on release properties and confirmed the bioactivity of the release product. Additionally, we observed that the effectiveness of CDC induction by DNX could be correlated to the GD2 expression level of the target cells, with both the intravenous DNX formulation and the released DNX. Collectively, these data highlights a strategy to overcome delivery challenges and potentially improve therapeutic efficacy in cells expressing heterogenous levels of GD2.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Development of a dinutuximab delivery system using silk foams for GD2 targeted neuroblastoma cell death

Ornell

Chiu

Coburn

2020

J Biomedical Materials Res

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“…In addition, on average the 10-50 mg/mL samples took up to 5 min to reconstitute while the 200 mg/mL samples took over 2 h to dissolve. Long reconstitution times have been commonly reported for high concentration protein solutions [26,27], and strategies for addressing this have been shared [7].…”

Section: Case Study 1: Effect Of Moisture Ingress and Excipient Ratiomentioning

confidence: 99%

The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG)

et al. 2020

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High protein concentration products for targeted therapeutic use are often freeze-dried to enhance stability. The long-term storage stability of freeze-dried (FD) plasma-derived Immunoglobulin G (IgG) from moderate to high concentrations (10–200 mg/mL) was assessed. Monomer content, binding activity and reconstitution times were evaluated over a 12-month period under accelerated and real-term storage conditions. In the first case study it was shown that FD IgG from 10 to 200 mg/mL had minimal monomer/activity losses at up to ambient temperature after 12 months of storage. However, at 45 °C the sucrose-to-protein ratio played a significant impact on IgG stability above 50 mg/mL. All IgG concentrations witnessed moisture ingress over a 12-month period. The impact of moisture ingress from environmental exposure (between 0.1% and 5% w/w moisture) for IgG 50 mg/mL was assessed, being generated by exposing low moisture batches to an atmospheric environment for fixed time periods. Results showed that at −20 °C and 20 °C there was no significant difference in terms of monomer or antigen-binding activity losses over 6 months. However, at 45 °C, there were losses in monomer content, seemingly worse for higher moisture content samples although model binding activity indicated no losses. Finally, the difference between a low moisture product (0.1–1% w/w) and a moderately high moisture (3% w/w) product generated by alternative freeze-drying cycles, both stoppered under low oxygen headspace conditions, was evaluated. Results showed that at −20 °C and 20 °C there was no difference in terms of binding activity or monomer content. However, at 45 °C, the low moisture samples had greater monomer and binding activity losses than samples from the highest moisture cycle batch, indicating that over-drying can be an issue.

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“…However, this is only possible so long as structural data are available for the protein under examination. Protein stability is also evaluated using freeze-drying and spray-drying [ 20 – 22 ]. In this section, we will focus on the stabilisation achieved by the use of additives to modify the microenvironment of the protein under investigation and the covalent immobilisation of proteins on to transducers.…”

Section: Protein Stabilisationmentioning

confidence: 99%

Bioconjugation and stabilisation of biomolecules in biosensors

Liébana

Drago

2016

Essays in Biochemistry

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Suitable bioconjugation strategies and stabilisation of biomolecules on electrodes is essential for the development of novel and commercially viable biosensors. In the present review, the functional groups that comprise the selectable targets for practical bioconjugation methods are discussed. We focus on describing the most common immobilisation techniques used in biosensor construction, which are classified into irreversible and reversible methods. Concerning the stability of proteins, the two main types of stability may be defined as (i) storage or shelf stability, and (ii) operational stability. Both types of stability are explained, as well as the introduction of an electrophoretic technique for predicting protein–polymer interactions. In addition, solution and dry stabilisation as well as stabilisation using the covalent immobilisation of proteins are discussed including possible factors that influence stability. Finally, the integration of nanomaterials, such as magnetic particles, with protein immobilisation is discussed in relation to protein stability studies.

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Stability of buffer-free freeze-dried formulations: A feasibility study of a monoclonal antibody at high protein concentrations

Cited by 34 publications

References 77 publications

Development of a dinutuximab delivery system using silk foams for GD2 targeted neuroblastoma cell death

Development of a dinutuximab delivery system using silk foams for GD2 targeted neuroblastoma cell death

The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG)

Bioconjugation and stabilisation of biomolecules in biosensors

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