Stabilisation of Recombinant Human Basic Fibroblast Growth Factor (FGF-2) against Stressors Encountered in Medicinal Product Processing and Evaluation

Basic fibroblast growth factor (FGF-2) is a highly labile protein with strong potential for tissue engineering. The aim of this study was to develop FGF-2 formulations that are stable against physical stressors encountered in pharmaceutical processing and evaluation. Pharmaceutical excipients, alone...

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Autores principales:	Leah R. Benington, Gunesh Rajan, Cornelia Locher, Lee Yong Lim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	fibroblast growth factor 2 basic fibroblast growth factor stabilisation thermal stability processing stability Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/a9be62efdaa34c7ea37779854c6c3095
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spelling	oai:doaj.org-article:a9be62efdaa34c7ea37779854c6c30952021-11-25T18:40:28ZStabilisation of Recombinant Human Basic Fibroblast Growth Factor (FGF-2) against Stressors Encountered in Medicinal Product Processing and Evaluation10.3390/pharmaceutics131117621999-4923https://doaj.org/article/a9be62efdaa34c7ea37779854c6c30952021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1762https://doaj.org/toc/1999-4923Basic fibroblast growth factor (FGF-2) is a highly labile protein with strong potential for tissue engineering. The aim of this study was to develop FGF-2 formulations that are stable against physical stressors encountered in pharmaceutical processing and evaluation. Pharmaceutical excipients, alone or in combination, were added to aqueous FGF-2 (770 ng/mL) solution and the stability of the resulting solutions on storage at 4–37 °C was evaluated. Stability of the solutions to repeated freeze-thaw cycles and lyophilisation was also evaluated, as well as the stability of the lyophilised stabilised protein to storage at −4, 4 and 18 °C for up to 12 months. In all of these experiments FGF-2 was quantified by ELISA assay. The as-received FGF-2, when dissolved in water, was highly unstable, retaining only 50% of baseline protein content after 30 min at 37 °C or 1 h at 25 °C. By contrast, FGF-2 solutions prepared with 0.5% <i>w/v</i> methylcellulose (MC) and 20 mM alanine (formulation F5) or with 0.5% <i>w/v</i> MC and 1 mg/mL human serum albumin (HSA) (formulation F6) were highly stable, having residual FGF-2 content comparable to baseline levels even after 2 h at 37 °C and 5 h at 25 °C. F5 and F6 were also highly stable to repeated freeze-thaw cycles, with >99% of FGF-2 load remaining after the third cycle. In addition, F5 and F6 were stable to lyophilisation, and the lyophilised products could be stored at −4, 4 or 18 °C for at least 12 months, with less than 1% loss in mean FGF-2 content. Thus, FGF-2 solution is effectively stabilised against both thermal and processing stressors in the presence of MC and alanine (F5), or MC and HSA (F6). The resultant FGF-2 solutions may be applied as medicinal products or further processed into more advanced medicinal products, e.g., scaffolds, for wound healing and tissue regeneration.Leah R. BeningtonGunesh RajanCornelia LocherLee Yong LimMDPI AGarticlefibroblast growth factor 2basic fibroblast growth factorstabilisationthermal stabilityprocessing stabilityPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1762, p 1762 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	fibroblast growth factor 2 basic fibroblast growth factor stabilisation thermal stability processing stability Pharmacy and materia medica RS1-441
spellingShingle	fibroblast growth factor 2 basic fibroblast growth factor stabilisation thermal stability processing stability Pharmacy and materia medica RS1-441 Leah R. Benington Gunesh Rajan Cornelia Locher Lee Yong Lim Stabilisation of Recombinant Human Basic Fibroblast Growth Factor (FGF-2) against Stressors Encountered in Medicinal Product Processing and Evaluation
description	Basic fibroblast growth factor (FGF-2) is a highly labile protein with strong potential for tissue engineering. The aim of this study was to develop FGF-2 formulations that are stable against physical stressors encountered in pharmaceutical processing and evaluation. Pharmaceutical excipients, alone or in combination, were added to aqueous FGF-2 (770 ng/mL) solution and the stability of the resulting solutions on storage at 4–37 °C was evaluated. Stability of the solutions to repeated freeze-thaw cycles and lyophilisation was also evaluated, as well as the stability of the lyophilised stabilised protein to storage at −4, 4 and 18 °C for up to 12 months. In all of these experiments FGF-2 was quantified by ELISA assay. The as-received FGF-2, when dissolved in water, was highly unstable, retaining only 50% of baseline protein content after 30 min at 37 °C or 1 h at 25 °C. By contrast, FGF-2 solutions prepared with 0.5% <i>w/v</i> methylcellulose (MC) and 20 mM alanine (formulation F5) or with 0.5% <i>w/v</i> MC and 1 mg/mL human serum albumin (HSA) (formulation F6) were highly stable, having residual FGF-2 content comparable to baseline levels even after 2 h at 37 °C and 5 h at 25 °C. F5 and F6 were also highly stable to repeated freeze-thaw cycles, with >99% of FGF-2 load remaining after the third cycle. In addition, F5 and F6 were stable to lyophilisation, and the lyophilised products could be stored at −4, 4 or 18 °C for at least 12 months, with less than 1% loss in mean FGF-2 content. Thus, FGF-2 solution is effectively stabilised against both thermal and processing stressors in the presence of MC and alanine (F5), or MC and HSA (F6). The resultant FGF-2 solutions may be applied as medicinal products or further processed into more advanced medicinal products, e.g., scaffolds, for wound healing and tissue regeneration.
format	article
author	Leah R. Benington Gunesh Rajan Cornelia Locher Lee Yong Lim
author_facet	Leah R. Benington Gunesh Rajan Cornelia Locher Lee Yong Lim
author_sort	Leah R. Benington
title	Stabilisation of Recombinant Human Basic Fibroblast Growth Factor (FGF-2) against Stressors Encountered in Medicinal Product Processing and Evaluation
title_short	Stabilisation of Recombinant Human Basic Fibroblast Growth Factor (FGF-2) against Stressors Encountered in Medicinal Product Processing and Evaluation
title_full	Stabilisation of Recombinant Human Basic Fibroblast Growth Factor (FGF-2) against Stressors Encountered in Medicinal Product Processing and Evaluation
title_fullStr	Stabilisation of Recombinant Human Basic Fibroblast Growth Factor (FGF-2) against Stressors Encountered in Medicinal Product Processing and Evaluation
title_full_unstemmed	Stabilisation of Recombinant Human Basic Fibroblast Growth Factor (FGF-2) against Stressors Encountered in Medicinal Product Processing and Evaluation
title_sort	stabilisation of recombinant human basic fibroblast growth factor (fgf-2) against stressors encountered in medicinal product processing and evaluation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a9be62efdaa34c7ea37779854c6c3095
work_keys_str_mv	AT leahrbenington stabilisationofrecombinanthumanbasicfibroblastgrowthfactorfgf2againststressorsencounteredinmedicinalproductprocessingandevaluation AT guneshrajan stabilisationofrecombinanthumanbasicfibroblastgrowthfactorfgf2againststressorsencounteredinmedicinalproductprocessingandevaluation AT cornelialocher stabilisationofrecombinanthumanbasicfibroblastgrowthfactorfgf2againststressorsencounteredinmedicinalproductprocessingandevaluation AT leeyonglim stabilisationofrecombinanthumanbasicfibroblastgrowthfactorfgf2againststressorsencounteredinmedicinalproductprocessingandevaluation
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Stabilisation of Recombinant Human Basic Fibroblast Growth Factor (FGF-2) against Stressors Encountered in Medicinal Product Processing and Evaluation

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