Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferase
Phenylketonuria (PKU) is a genetic metabolic disorder caused by an enzyme deficiency that leads to the accumulation of phenylalanine, which can cause neurotoxicity and several other problems. A potential alternative to the universal standard treatment based on a lifelong protein-restricted diet, is...
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Elsevier
2025-08-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425005575 |
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| author | Daniel Abella-López Adrián López-Teijeiro Tomás Pose-Boirazian Natalia Barreiro-Piñeiro José M. Martínez-Costas |
| author_facet | Daniel Abella-López Adrián López-Teijeiro Tomás Pose-Boirazian Natalia Barreiro-Piñeiro José M. Martínez-Costas |
| author_sort | Daniel Abella-López |
| collection | DOAJ |
| description | Phenylketonuria (PKU) is a genetic metabolic disorder caused by an enzyme deficiency that leads to the accumulation of phenylalanine, which can cause neurotoxicity and several other problems. A potential alternative to the universal standard treatment based on a lifelong protein-restricted diet, is the development of oral replacement therapies using phenylalanine ammonia lyase from Anabaena variabilis (AvPAL). However, oral administration of polypeptides presents a major challenge due to gastrointestinal (GI) instability. To address this issue, the use of the IC-Tagging system as an advanced one step, in cellulo nanosphere (NS)-encapsulation strategy for protein stabilization and oral delivery is proposed. A highly active version of AvPAL was produced to which nanoencapsulation provides formidable thermostability, resistance to acidic pH, long-term storage stability and protection against proteolytic degradation. This latter characteristic, essential for oral delivery of polypeptides, is further enhanced by coating with chitosan the NS-encapsulated enzyme. Thus, a similarly nanoencapsulated and chitosan-coated luciferase displays sustained enzymatic activity through the entire GI transit when administered orally in mice, indicating the high protective capability of the system while maintaining the availability of the enzyme. Overall, these results highlight the potential and versatility for peptide-based oral delivery applications of this innovative methodology. |
| format | Article |
| id | doaj-art-4f0ba098af2e4b3db3b65859cb4bec58 |
| institution | DOAJ |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-4f0ba098af2e4b3db3b65859cb4bec582025-08-20T03:21:55ZengElsevierMaterials Today Bio2590-00642025-08-013310198710.1016/j.mtbio.2025.101987Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferaseDaniel Abella-López0Adrián López-Teijeiro1Tomás Pose-Boirazian2Natalia Barreiro-Piñeiro3José M. Martínez-Costas4Department of Biochemistry and Molecular Biology and Center for Research in Biological Chemistry and Molecular Materials (CIQUS), University of Santiago de Compostela, C/ Jerónimo de la Fuente S/N, 15782, Santiago de Compostela, SpainDepartment of Biochemistry and Molecular Biology and Center for Research in Biological Chemistry and Molecular Materials (CIQUS), University of Santiago de Compostela, C/ Jerónimo de la Fuente S/N, 15782, Santiago de Compostela, SpainDepartment of Biochemistry and Molecular Biology and Center for Research in Biological Chemistry and Molecular Materials (CIQUS), University of Santiago de Compostela, C/ Jerónimo de la Fuente S/N, 15782, Santiago de Compostela, SpainDepartment of Biochemistry and Molecular Biology and Center for Research in Biological Chemistry and Molecular Materials (CIQUS), University of Santiago de Compostela, C/ Jerónimo de la Fuente S/N, 15782, Santiago de Compostela, SpainCorresponding author.; Department of Biochemistry and Molecular Biology and Center for Research in Biological Chemistry and Molecular Materials (CIQUS), University of Santiago de Compostela, C/ Jerónimo de la Fuente S/N, 15782, Santiago de Compostela, SpainPhenylketonuria (PKU) is a genetic metabolic disorder caused by an enzyme deficiency that leads to the accumulation of phenylalanine, which can cause neurotoxicity and several other problems. A potential alternative to the universal standard treatment based on a lifelong protein-restricted diet, is the development of oral replacement therapies using phenylalanine ammonia lyase from Anabaena variabilis (AvPAL). However, oral administration of polypeptides presents a major challenge due to gastrointestinal (GI) instability. To address this issue, the use of the IC-Tagging system as an advanced one step, in cellulo nanosphere (NS)-encapsulation strategy for protein stabilization and oral delivery is proposed. A highly active version of AvPAL was produced to which nanoencapsulation provides formidable thermostability, resistance to acidic pH, long-term storage stability and protection against proteolytic degradation. This latter characteristic, essential for oral delivery of polypeptides, is further enhanced by coating with chitosan the NS-encapsulated enzyme. Thus, a similarly nanoencapsulated and chitosan-coated luciferase displays sustained enzymatic activity through the entire GI transit when administered orally in mice, indicating the high protective capability of the system while maintaining the availability of the enzyme. Overall, these results highlight the potential and versatility for peptide-based oral delivery applications of this innovative methodology.http://www.sciencedirect.com/science/article/pii/S2590006425005575Oral peptide deliveryProtein stabilizationIC-TaggingPhenylketonuriaEnzyme replacement therapyAvPAL |
| spellingShingle | Daniel Abella-López Adrián López-Teijeiro Tomás Pose-Boirazian Natalia Barreiro-Piñeiro José M. Martínez-Costas Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferase Materials Today Bio Oral peptide delivery Protein stabilization IC-Tagging Phenylketonuria Enzyme replacement therapy AvPAL |
| title | Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferase |
| title_full | Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferase |
| title_fullStr | Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferase |
| title_full_unstemmed | Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferase |
| title_short | Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferase |
| title_sort | nanoencapsulation platform for oral delivery of peptides in vitro stabilization of avpal and formulation of a gastrointestinal resistant luciferase |
| topic | Oral peptide delivery Protein stabilization IC-Tagging Phenylketonuria Enzyme replacement therapy AvPAL |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425005575 |
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