Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity
Violacein (Viol) is a bacterial purple water-insoluble pigment synthesized by Chromobacterium violaceum and other microorganisms that display many beneficial therapeutic properties including anticancer activity. Viol was produced, purified in our laboratory, and encapsulated in a nanostructured lipi...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.914126/full |
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| author | Ignacio Rivero Berti Boris E. Rodenak-Kladniew Sergio F. Katz Eva Carolina Arrua Eva Carolina Arrua Vera A. Alvarez Nelson Duran Nelson Duran Guillermo R. Castro Guillermo R. Castro |
| author_facet | Ignacio Rivero Berti Boris E. Rodenak-Kladniew Sergio F. Katz Eva Carolina Arrua Eva Carolina Arrua Vera A. Alvarez Nelson Duran Nelson Duran Guillermo R. Castro Guillermo R. Castro |
| author_sort | Ignacio Rivero Berti |
| collection | DOAJ |
| description | Violacein (Viol) is a bacterial purple water-insoluble pigment synthesized by Chromobacterium violaceum and other microorganisms that display many beneficial therapeutic properties including anticancer activity. Viol was produced, purified in our laboratory, and encapsulated in a nanostructured lipid carrier (NLC). The NLC is composed of the solid lipid myristyl myristate, an oily lipid mixture composed of capric and caprylic acids, and the surfactant poloxamer P188. Dormant lipase from Rhizomucor miehei was incorporated into the NLC-Viol to develop an active release system. The NLC particle size determined by dynamic light scattering brings around 150 nm particle size and ζ≈ −9.0 mV with or without lipase, but the incorporation of lipase increase the PdI from 0.241 to 0.319 (≈32%). For scaffold development, a 2.5 hydroxypropyl methylcellulose/chitosan ratio was obtained after optimization of a composite for extrusion in a 3D-bioprinter developed and constructed in our laboratory. Final Viol encapsulation efficiency in the printings was over 90%. Kinetic release of the biodye at pH = 7.4 from the mesh containing NLC-lipase showed roughly 20% Viol fast release than without the enzyme. However, both Viol kinetic releases displayed similar profiles at pH = 5.0, where the lipase is inactive. The kinetic release of Viol from the NLC-matrices was modeled and the best correlation was found with the Korsmeyer-Peppas model (R2 = 0.95) with n < 0.5 suggesting a Fickian release of Viol from the matrices. Scanning Electron Microscope (SEM) images of the NLC-meshes showed significant differences before and after Viol’s release. Also, the presence of lipase dramatically increased the gaps in the interchain mesh. XRD and Fourier Transform Infrared (FTIR) analyses of the NLC-meshes showed a decrease in the crystalline structure of the composites with the incorporation of the NLC, and the decrease of myristyl myristate in the mesh can be attributed to the lipase activity. TGA profiles of the NLC-meshes showed high thermal stability than the individual components. Cytotoxic studies in A549 and HCT-116 cancer cell lines revealed high anticancer activity of the matrix mediated by mucoadhesive chitosan, plus the biological synergistic activities of violacein and lipase. |
| first_indexed | 2024-12-11T03:27:01Z |
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| id | doaj.art-e4b2bd49070d413f85e46fbcfc05b6aa |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-11T03:27:01Z |
| publishDate | 2022-07-01 |
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| spelling | doaj.art-e4b2bd49070d413f85e46fbcfc05b6aa2022-12-22T01:22:28ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-07-011010.3389/fchem.2022.914126914126Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer ActivityIgnacio Rivero Berti0Boris E. Rodenak-Kladniew1Sergio F. Katz2Eva Carolina Arrua3Eva Carolina Arrua4Vera A. Alvarez5Nelson Duran6Nelson Duran7Guillermo R. Castro8Guillermo R. Castro9Laboratorio de Nanobiomateriale, CINDEFI, Departamento de Química, Facultad de Ciencias Exactas, CONICET (CCT La Plata), Universidad Nacional de La Plata (UNLP), La Plata, ArgentinaInstituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, CCT-La Plata, Facultad de Ciencias Médicas, La Plata, ArgentinaLaboratorio de Nanobiomateriale, CINDEFI, Departamento de Química, Facultad de Ciencias Exactas, CONICET (CCT La Plata), Universidad Nacional de La Plata (UNLP), La Plata, ArgentinaMax Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC), Partner Laboratory of the Max Planck Institute for Biophysical Chemistry (MPIbpC, MPG), Centro de Estudios Interdisciplinarios (CEI), Universidad Nacional de Rosario, Rosario, ArgentinaCentro de Investigación y Desarrollo en Materiales Avanzados y Almacenamiento de Energía de Jujuy-Univ. Nac., de Jujuy, ArgentinaGrupo de Materiales Compuestos Termoplásticos (CoMP), Instituto de Investigaciones en Ciencia y Tecnología de Materiales (INTEMA), Facultad de Ingeniería, Universidad Nacional de Mar del Plata (UNMDP), CONICET, Mar del Plata, ArgentinaLaboratory of Urogenital Carcinogenesis and Immunotherapy, Department of Structural and Functional Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, BrazilNanomedicine Research Unit (Nanomed), Center for Natural and Human Sciences (CCNH), Universidade Federal do ABC (UFABC), Santo André, BrazilMax Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC), Partner Laboratory of the Max Planck Institute for Biophysical Chemistry (MPIbpC, MPG), Centro de Estudios Interdisciplinarios (CEI), Universidad Nacional de Rosario, Rosario, ArgentinaNanomedicine Research Unit (Nanomed), Center for Natural and Human Sciences (CCNH), Universidade Federal do ABC (UFABC), Santo André, BrazilViolacein (Viol) is a bacterial purple water-insoluble pigment synthesized by Chromobacterium violaceum and other microorganisms that display many beneficial therapeutic properties including anticancer activity. Viol was produced, purified in our laboratory, and encapsulated in a nanostructured lipid carrier (NLC). The NLC is composed of the solid lipid myristyl myristate, an oily lipid mixture composed of capric and caprylic acids, and the surfactant poloxamer P188. Dormant lipase from Rhizomucor miehei was incorporated into the NLC-Viol to develop an active release system. The NLC particle size determined by dynamic light scattering brings around 150 nm particle size and ζ≈ −9.0 mV with or without lipase, but the incorporation of lipase increase the PdI from 0.241 to 0.319 (≈32%). For scaffold development, a 2.5 hydroxypropyl methylcellulose/chitosan ratio was obtained after optimization of a composite for extrusion in a 3D-bioprinter developed and constructed in our laboratory. Final Viol encapsulation efficiency in the printings was over 90%. Kinetic release of the biodye at pH = 7.4 from the mesh containing NLC-lipase showed roughly 20% Viol fast release than without the enzyme. However, both Viol kinetic releases displayed similar profiles at pH = 5.0, where the lipase is inactive. The kinetic release of Viol from the NLC-matrices was modeled and the best correlation was found with the Korsmeyer-Peppas model (R2 = 0.95) with n < 0.5 suggesting a Fickian release of Viol from the matrices. Scanning Electron Microscope (SEM) images of the NLC-meshes showed significant differences before and after Viol’s release. Also, the presence of lipase dramatically increased the gaps in the interchain mesh. XRD and Fourier Transform Infrared (FTIR) analyses of the NLC-meshes showed a decrease in the crystalline structure of the composites with the incorporation of the NLC, and the decrease of myristyl myristate in the mesh can be attributed to the lipase activity. TGA profiles of the NLC-meshes showed high thermal stability than the individual components. Cytotoxic studies in A549 and HCT-116 cancer cell lines revealed high anticancer activity of the matrix mediated by mucoadhesive chitosan, plus the biological synergistic activities of violacein and lipase.https://www.frontiersin.org/articles/10.3389/fchem.2022.914126/fullViolaceinnanostructured lipid carriersLipasechitosan3D-bioprintercontrolled release |
| spellingShingle | Ignacio Rivero Berti Boris E. Rodenak-Kladniew Sergio F. Katz Eva Carolina Arrua Eva Carolina Arrua Vera A. Alvarez Nelson Duran Nelson Duran Guillermo R. Castro Guillermo R. Castro Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity Frontiers in Chemistry Violacein nanostructured lipid carriers Lipase chitosan 3D-bioprinter controlled release |
| title | Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity |
| title_full | Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity |
| title_fullStr | Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity |
| title_full_unstemmed | Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity |
| title_short | Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity |
| title_sort | enzymatic active release of violacein present in nanostructured lipid carrier by lipase encapsulated in 3d bioprinted chitosan hydroxypropyl methylcellulose matrix with anticancer activity |
| topic | Violacein nanostructured lipid carriers Lipase chitosan 3D-bioprinter controlled release |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.914126/full |
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