Self-buffering capacity of a human sulfatase for central nervous system delivery
| Autor: | Keethkumar Jain, Nazila Salamat-Miller, Katherine Taylor, Yi Wen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0106 biological sciences
0301 basic medicine Central Nervous System Science Central nervous system Intrathecal space Biologics Buffers 01 natural sciences Article Phosphates Recombinant protein therapy 03 medical and health sciences Drug Delivery Systems 010608 biotechnology medicine Humans High concentration Multidisciplinary Chemistry Protein Stability Sulfatase Protein delivery Proteins Enzymes Solutions 030104 developmental biology medicine.anatomical_structure Drug delivery Biophysics Medicine Sulfatases Peptides |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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