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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/11/11/2946 |
| _version_ | 1827675827929612288 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:13:16Z |
| format | Article |
| id | doaj.art-cc555f7c1aad443e92d62c80b5e4a3f9 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-10T05:13:16Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-cc555f7c1aad443e92d62c80b5e4a3f92023-11-23T00:40:49ZengMDPI AGNanomaterials2079-49912021-11-011111294610.3390/nano11112946Tween<sup>®</sup> Preserves Enzyme Activity and Stability in PLGA NanoparticlesJason Thomas Duskey0Ilaria Ottonelli1Arianna Rinaldi2Irene Parmeggiani3Barbara Zambelli4Leon Z. Wang5Robert K. Prud’homme6Maria Angela Vandelli7Giovanni Tosi8Barbara Ruozi9Te.Far.T.I.-Nanotech Lab, Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyTe.Far.T.I.-Nanotech Lab, Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyTe.Far.T.I.-Nanotech Lab, Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyTe.Far.T.I.-Nanotech Lab, Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyLaboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, 40127 Bologna, ItalyDepartment of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USADepartment of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USATe.Far.T.I.-Nanotech Lab, Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyTe.Far.T.I.-Nanotech Lab, Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyTe.Far.T.I.-Nanotech Lab, Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyEnzymes, 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.https://www.mdpi.com/2079-4991/11/11/2946polymeric nanoparticlesenzyme deliveryenzyme stabilizationTween<sup>®</sup> stabilizationnanomedicine |
| spellingShingle | 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 Nanomaterials polymeric nanoparticles enzyme delivery enzyme stabilization Tween<sup>®</sup> stabilization nanomedicine |
| title | 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_short | Tween<sup>®</sup> Preserves Enzyme Activity and Stability in PLGA Nanoparticles |
| title_sort | tween sup r sup preserves enzyme activity and stability in plga nanoparticles |
| topic | polymeric nanoparticles enzyme delivery enzyme stabilization Tween<sup>®</sup> stabilization nanomedicine |
| url | https://www.mdpi.com/2079-4991/11/11/2946 |
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