Tween<sup>®</sup> Preserves Enzyme Activity and Stability in PLGA Nanoparticles

Enzymes, as natural and potentially long-term treatment options, have become one of the most sought-after pharmaceutical molecules to be delivered with nanoparticles (NPs); however, their instability during formulation often leads to underwhelming results. Various molecules, including the Tween<s...

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Autores principales:	Jason Thomas Duskey, Ilaria Ottonelli, Arianna Rinaldi, Irene Parmeggiani, Barbara Zambelli, Leon Z. Wang, Robert K. Prud’homme, Maria Angela Vandelli, Giovanni Tosi, Barbara Ruozi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	polymeric nanoparticles enzyme delivery enzyme stabilization Tween<sup>®</sup> stabilization nanomedicine Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/cc555f7c1aad443e92d62c80b5e4a3f9
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spelling	oai:doaj.org-article:cc555f7c1aad443e92d62c80b5e4a3f92021-11-25T18:31:04ZTween<sup>®</sup> Preserves Enzyme Activity and Stability in PLGA Nanoparticles10.3390/nano111129462079-4991https://doaj.org/article/cc555f7c1aad443e92d62c80b5e4a3f92021-11-01T00:00:00Zhttps://www.mdpi.com/2079-4991/11/11/2946https://doaj.org/toc/2079-4991Enzymes, as natural and potentially long-term treatment options, have become one of the most sought-after pharmaceutical molecules to be delivered with nanoparticles (NPs); however, their instability during formulation often leads to underwhelming results. Various molecules, including the Tween<sup>®</sup> polysorbate series, have demonstrated enzyme activity protection but are often used uncontrolled without optimization. Here, poly(lactic-co-glycolic) acid (PLGA) NPs loaded with β-glucosidase (β-Glu) solutions containing Tween<sup>®</sup> 20, 60, or 80 were compared. Mixing the enzyme with Tween<sup>®</sup> pre-formulation had no effect on particle size or physical characteristics, but increased the amount of enzyme loaded. More importantly, NPs made with Tween<sup>®</sup> 20:enzyme solutions maintained significantly higher enzyme activity. Therefore, Tween<sup>®</sup> 20:enzyme solutions ranging from 60:1 to 2419:1 mol:mol were further analyzed. Isothermal titration calorimetry analysis demonstrated low affinity and unquantifiable binding between Tween<sup>®</sup> 20 and β-Glu. Incorporating these solutions in NPs showed no effect on size, zeta potential, or morphology. The amount of enzyme and Tween<sup>®</sup> 20 in the NPs was constant for all samples, but a trend towards higher activity with higher molar rapports of Tween<sup>®</sup> 20:β-Glu was observed. Finally, a burst release from NPs in the first hour with Tween<sup>®</sup>:β-Glu solutions was the same as free enzyme, but the enzyme remained active longer in solution. These results highlight the importance of stabilizers during NP formulation and how optimizing their use to stabilize an enzyme can help researchers design more efficient and effective enzyme loaded NPs.Jason Thomas DuskeyIlaria OttonelliArianna RinaldiIrene ParmeggianiBarbara ZambelliLeon Z. WangRobert K. Prud’hommeMaria Angela VandelliGiovanni TosiBarbara RuoziMDPI AGarticlepolymeric nanoparticlesenzyme deliveryenzyme stabilizationTween<sup>®</sup> stabilizationnanomedicineChemistryQD1-999ENNanomaterials, Vol 11, Iss 2946, p 2946 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	polymeric nanoparticles enzyme delivery enzyme stabilization Tween<sup>®</sup> stabilization nanomedicine Chemistry QD1-999
spellingShingle	polymeric nanoparticles enzyme delivery enzyme stabilization Tween<sup>®</sup> stabilization nanomedicine Chemistry QD1-999 Jason Thomas Duskey Ilaria Ottonelli Arianna Rinaldi Irene Parmeggiani Barbara Zambelli Leon Z. Wang Robert K. Prud’homme Maria Angela Vandelli Giovanni Tosi Barbara Ruozi Tween<sup>®</sup> Preserves Enzyme Activity and Stability in PLGA Nanoparticles
description	Enzymes, as natural and potentially long-term treatment options, have become one of the most sought-after pharmaceutical molecules to be delivered with nanoparticles (NPs); however, their instability during formulation often leads to underwhelming results. Various molecules, including the Tween<sup>®</sup> polysorbate series, have demonstrated enzyme activity protection but are often used uncontrolled without optimization. Here, poly(lactic-co-glycolic) acid (PLGA) NPs loaded with β-glucosidase (β-Glu) solutions containing Tween<sup>®</sup> 20, 60, or 80 were compared. Mixing the enzyme with Tween<sup>®</sup> pre-formulation had no effect on particle size or physical characteristics, but increased the amount of enzyme loaded. More importantly, NPs made with Tween<sup>®</sup> 20:enzyme solutions maintained significantly higher enzyme activity. Therefore, Tween<sup>®</sup> 20:enzyme solutions ranging from 60:1 to 2419:1 mol:mol were further analyzed. Isothermal titration calorimetry analysis demonstrated low affinity and unquantifiable binding between Tween<sup>®</sup> 20 and β-Glu. Incorporating these solutions in NPs showed no effect on size, zeta potential, or morphology. The amount of enzyme and Tween<sup>®</sup> 20 in the NPs was constant for all samples, but a trend towards higher activity with higher molar rapports of Tween<sup>®</sup> 20:β-Glu was observed. Finally, a burst release from NPs in the first hour with Tween<sup>®</sup>:β-Glu solutions was the same as free enzyme, but the enzyme remained active longer in solution. These results highlight the importance of stabilizers during NP formulation and how optimizing their use to stabilize an enzyme can help researchers design more efficient and effective enzyme loaded NPs.
format	article
author	Jason Thomas Duskey Ilaria Ottonelli Arianna Rinaldi Irene Parmeggiani Barbara Zambelli Leon Z. Wang Robert K. Prud’homme Maria Angela Vandelli Giovanni Tosi Barbara Ruozi
author_facet	Jason Thomas Duskey Ilaria Ottonelli Arianna Rinaldi Irene Parmeggiani Barbara Zambelli Leon Z. Wang Robert K. Prud’homme Maria Angela Vandelli Giovanni Tosi Barbara Ruozi
author_sort	Jason Thomas Duskey
title	Tween<sup>®</sup> Preserves Enzyme Activity and Stability in PLGA Nanoparticles
title_short	Tween<sup>®</sup> Preserves Enzyme Activity and Stability in PLGA Nanoparticles
title_full	Tween<sup>®</sup> Preserves Enzyme Activity and Stability in PLGA Nanoparticles
title_fullStr	Tween<sup>®</sup> Preserves Enzyme Activity and Stability in PLGA Nanoparticles
title_full_unstemmed	Tween<sup>®</sup> Preserves Enzyme Activity and Stability in PLGA Nanoparticles
title_sort	tween<sup>®</sup> preserves enzyme activity and stability in plga nanoparticles
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cc555f7c1aad443e92d62c80b5e4a3f9
work_keys_str_mv	AT jasonthomasduskey tweensupsuppreservesenzymeactivityandstabilityinplgananoparticles AT ilariaottonelli tweensupsuppreservesenzymeactivityandstabilityinplgananoparticles AT ariannarinaldi tweensupsuppreservesenzymeactivityandstabilityinplgananoparticles AT ireneparmeggiani tweensupsuppreservesenzymeactivityandstabilityinplgananoparticles AT barbarazambelli tweensupsuppreservesenzymeactivityandstabilityinplgananoparticles AT leonzwang tweensupsuppreservesenzymeactivityandstabilityinplgananoparticles AT robertkprudhomme tweensupsuppreservesenzymeactivityandstabilityinplgananoparticles AT mariaangelavandelli tweensupsuppreservesenzymeactivityandstabilityinplgananoparticles AT giovannitosi tweensupsuppreservesenzymeactivityandstabilityinplgananoparticles AT barbararuozi tweensupsuppreservesenzymeactivityandstabilityinplgananoparticles
_version_	1718411044644192256

Tween<sup>®</sup> Preserves Enzyme Activity and Stability in PLGA Nanoparticles

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