Self-buffering capacity of a human sulfatase for central nervous system delivery

Abstract Direct delivery of therapeutic enzymes to the Central Nervous System requires stringent formulation design. Not only should the formulation design consider the delicate balance of existing ions, proteins, and osmolality in the cerebrospinal fluid, it must also provide long term efficacy and...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yi Wen, Nazila Salamat-Miller, Keethkumar Jain, Katherine Taylor
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1400d1c04e6a4582b16f39e102a5ed4b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1400d1c04e6a4582b16f39e102a5ed4b
record_format	dspace
spelling	oai:doaj.org-article:1400d1c04e6a4582b16f39e102a5ed4b2021-12-02T11:45:04ZSelf-buffering capacity of a human sulfatase for central nervous system delivery10.1038/s41598-021-86178-22045-2322https://doaj.org/article/1400d1c04e6a4582b16f39e102a5ed4b2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86178-2https://doaj.org/toc/2045-2322Abstract Direct delivery of therapeutic enzymes to the Central Nervous System requires stringent formulation design. Not only should the formulation design consider the delicate balance of existing ions, proteins, and osmolality in the cerebrospinal fluid, it must also provide long term efficacy and stability for the enzyme. One fundamental approach to this predicament is designing formulations with no buffering species. In this study, we report a high concentration, saline-based formulation for a human sulfatase for its delivery into the intrathecal space. A high concentration formulation (≤ 40 mg/mL) was developed through a series of systematic studies that demonstrated the feasibility of a self-buffered formulation for this molecule. The self-buffering capacity phenomenon was found to be a product of both the protein itself and potentially the residual phosphates associated with the protein. To date, the self-buffered formulation for this molecule has been stable for up to 4 years when stored at 5 ± 3 °C, with no changes either in the pH values or other quality attributes of the molecule. The high concentration self-buffered protein formulation was also observed to be stable when exposed to multiple freeze–thaw cycles and was robust during in-use and agitation studies.Yi WenNazila Salamat-MillerKeethkumar JainKatherine TaylorNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yi Wen Nazila Salamat-Miller Keethkumar Jain Katherine Taylor Self-buffering capacity of a human sulfatase for central nervous system delivery
description	Abstract Direct delivery of therapeutic enzymes to the Central Nervous System requires stringent formulation design. Not only should the formulation design consider the delicate balance of existing ions, proteins, and osmolality in the cerebrospinal fluid, it must also provide long term efficacy and stability for the enzyme. One fundamental approach to this predicament is designing formulations with no buffering species. In this study, we report a high concentration, saline-based formulation for a human sulfatase for its delivery into the intrathecal space. A high concentration formulation (≤ 40 mg/mL) was developed through a series of systematic studies that demonstrated the feasibility of a self-buffered formulation for this molecule. The self-buffering capacity phenomenon was found to be a product of both the protein itself and potentially the residual phosphates associated with the protein. To date, the self-buffered formulation for this molecule has been stable for up to 4 years when stored at 5 ± 3 °C, with no changes either in the pH values or other quality attributes of the molecule. The high concentration self-buffered protein formulation was also observed to be stable when exposed to multiple freeze–thaw cycles and was robust during in-use and agitation studies.
format	article
author	Yi Wen Nazila Salamat-Miller Keethkumar Jain Katherine Taylor
author_facet	Yi Wen Nazila Salamat-Miller Keethkumar Jain Katherine Taylor
author_sort	Yi Wen
title	Self-buffering capacity of a human sulfatase for central nervous system delivery
title_short	Self-buffering capacity of a human sulfatase for central nervous system delivery
title_full	Self-buffering capacity of a human sulfatase for central nervous system delivery
title_fullStr	Self-buffering capacity of a human sulfatase for central nervous system delivery
title_full_unstemmed	Self-buffering capacity of a human sulfatase for central nervous system delivery
title_sort	self-buffering capacity of a human sulfatase for central nervous system delivery
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1400d1c04e6a4582b16f39e102a5ed4b
work_keys_str_mv	AT yiwen selfbufferingcapacityofahumansulfataseforcentralnervoussystemdelivery AT nazilasalamatmiller selfbufferingcapacityofahumansulfataseforcentralnervoussystemdelivery AT keethkumarjain selfbufferingcapacityofahumansulfataseforcentralnervoussystemdelivery AT katherinetaylor selfbufferingcapacityofahumansulfataseforcentralnervoussystemdelivery
_version_	1718395266326855680

Self-buffering capacity of a human sulfatase for central nervous system delivery

Ejemplares similares