Nanoencapsulation as a General Solution for Lyophilization of Labile Substrates

Protein macromolecules occur naturally at the nanoscale. The use of a dedicated nanoparticle as a lyophilization excipient, however, has not been reported. Because biopolymeric and lipid nanoparticles often denature protein macromolecules and commonly lack the structural rigidity to survive the free...

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Autores principales:	Girish Vallerinteavide Mavelli, Samira Sadeghi, Siddhesh Sujit Vaidya, Shik Nie Kong, Chester Lee Drum
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	lyophilization freeze-drying thermostable exoshells tES HRP Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/dd763b45a61d413ba6f315325ad32bc4
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spelling	oai:doaj.org-article:dd763b45a61d413ba6f315325ad32bc42021-11-25T18:40:43ZNanoencapsulation as a General Solution for Lyophilization of Labile Substrates10.3390/pharmaceutics131117901999-4923https://doaj.org/article/dd763b45a61d413ba6f315325ad32bc42021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1790https://doaj.org/toc/1999-4923Protein macromolecules occur naturally at the nanoscale. The use of a dedicated nanoparticle as a lyophilization excipient, however, has not been reported. Because biopolymeric and lipid nanoparticles often denature protein macromolecules and commonly lack the structural rigidity to survive the freeze-drying process, we hypothesized that surrounding an individual protein substrate with a nanoscale, thermostable exoshell (tES) would prevent aggregation and protect the substrate from denaturation during freezing, sublimation, and storage. We systematically investigated the properties of tES, including secondary structure and its homogeneity, throughout the process of lyophilization and found that tES have a near 100% recovery following aqueous reconstitution. We then tested the hypothesis that tES could encapsulate a model substrate, horseradish peroxidase (HRP), using charge complementation and pH-mediated controlled assembly. HRP were encapsulated within the 8 nm internal tES aqueous cavity using a simplified loading procedure. Time-course experiments demonstrated that unprotected HRP loses 95% of activity after 1 month of lyophilized storage. After encapsulation within tES nanoparticles, 70% of HRP activity was recovered, representing a 14-fold improvement and this effect was reproducible across a range of storage temperatures. To our knowledge, these results represent the first reported use of nanoparticle encapsulation to stabilize a functional macromolecule during lyophilization. Thermostable nanoencapsulation may be a useful method for the long-term storage of labile proteins.Girish Vallerinteavide MavelliSamira SadeghiSiddhesh Sujit VaidyaShik Nie KongChester Lee DrumMDPI AGarticlelyophilizationfreeze-dryingthermostable exoshellstESHRPPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1790, p 1790 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lyophilization freeze-drying thermostable exoshells tES HRP Pharmacy and materia medica RS1-441
spellingShingle	lyophilization freeze-drying thermostable exoshells tES HRP Pharmacy and materia medica RS1-441 Girish Vallerinteavide Mavelli Samira Sadeghi Siddhesh Sujit Vaidya Shik Nie Kong Chester Lee Drum Nanoencapsulation as a General Solution for Lyophilization of Labile Substrates
description	Protein macromolecules occur naturally at the nanoscale. The use of a dedicated nanoparticle as a lyophilization excipient, however, has not been reported. Because biopolymeric and lipid nanoparticles often denature protein macromolecules and commonly lack the structural rigidity to survive the freeze-drying process, we hypothesized that surrounding an individual protein substrate with a nanoscale, thermostable exoshell (tES) would prevent aggregation and protect the substrate from denaturation during freezing, sublimation, and storage. We systematically investigated the properties of tES, including secondary structure and its homogeneity, throughout the process of lyophilization and found that tES have a near 100% recovery following aqueous reconstitution. We then tested the hypothesis that tES could encapsulate a model substrate, horseradish peroxidase (HRP), using charge complementation and pH-mediated controlled assembly. HRP were encapsulated within the 8 nm internal tES aqueous cavity using a simplified loading procedure. Time-course experiments demonstrated that unprotected HRP loses 95% of activity after 1 month of lyophilized storage. After encapsulation within tES nanoparticles, 70% of HRP activity was recovered, representing a 14-fold improvement and this effect was reproducible across a range of storage temperatures. To our knowledge, these results represent the first reported use of nanoparticle encapsulation to stabilize a functional macromolecule during lyophilization. Thermostable nanoencapsulation may be a useful method for the long-term storage of labile proteins.
format	article
author	Girish Vallerinteavide Mavelli Samira Sadeghi Siddhesh Sujit Vaidya Shik Nie Kong Chester Lee Drum
author_facet	Girish Vallerinteavide Mavelli Samira Sadeghi Siddhesh Sujit Vaidya Shik Nie Kong Chester Lee Drum
author_sort	Girish Vallerinteavide Mavelli
title	Nanoencapsulation as a General Solution for Lyophilization of Labile Substrates
title_short	Nanoencapsulation as a General Solution for Lyophilization of Labile Substrates
title_full	Nanoencapsulation as a General Solution for Lyophilization of Labile Substrates
title_fullStr	Nanoencapsulation as a General Solution for Lyophilization of Labile Substrates
title_full_unstemmed	Nanoencapsulation as a General Solution for Lyophilization of Labile Substrates
title_sort	nanoencapsulation as a general solution for lyophilization of labile substrates
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/dd763b45a61d413ba6f315325ad32bc4
work_keys_str_mv	AT girishvallerinteavidemavelli nanoencapsulationasageneralsolutionforlyophilizationoflabilesubstrates AT samirasadeghi nanoencapsulationasageneralsolutionforlyophilizationoflabilesubstrates AT siddheshsujitvaidya nanoencapsulationasageneralsolutionforlyophilizationoflabilesubstrates AT shikniekong nanoencapsulationasageneralsolutionforlyophilizationoflabilesubstrates AT chesterleedrum nanoencapsulationasageneralsolutionforlyophilizationoflabilesubstrates
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Nanoencapsulation as a General Solution for Lyophilization of Labile Substrates

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