On-Chip Synthesis of Hyaluronic Acid-Based Nanoparticles for Selective Inhibition of CD44+ Human Mesenchymal Stem Cell Proliferation
In this study, an innovative microfluidics-based method was developed for one-step synthesis of hyaluronic acid (HA)-based nanoparticles (NPs), by exploiting polyelectrolytic interactions between HA and chitosan (CS), in order to improve reliability, reproducibility and possible scale-up of the NPs...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/3/260 |
| _version_ | 1811297968920199168 |
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| author | Enrica Chiesa Federica Riva Rossella Dorati Antonietta Greco Stefania Ricci Silvia Pisani Maddalena Patrini Tiziana Modena Bice Conti Ida Genta |
| author_facet | Enrica Chiesa Federica Riva Rossella Dorati Antonietta Greco Stefania Ricci Silvia Pisani Maddalena Patrini Tiziana Modena Bice Conti Ida Genta |
| author_sort | Enrica Chiesa |
| collection | DOAJ |
| description | In this study, an innovative microfluidics-based method was developed for one-step synthesis of hyaluronic acid (HA)-based nanoparticles (NPs), by exploiting polyelectrolytic interactions between HA and chitosan (CS), in order to improve reliability, reproducibility and possible scale-up of the NPs preparation. The on-chip synthesis, using a staggered herringbone micromixer, allowed to produce HA/CS NPs with tailored-made size and suitable for both parenteral (117.50 ± 4.51 nm) and loco-regional (349.15 ± 38.09 nm) administration, mainly composed by HA (more than 85% wt) with high negative surface charge (< −20 mV). HA/CS NPs were successfully loaded with a challenging water-insoluble molecule, Everolimus (EVE), an FDA- and EMA-approved anticancer drug able to lead to cell cycle arrest, reduced angiogenesis and promotion of apoptosis. HA/CS NPs resulted to be massively internalized in CD44+ human mesenchymal stem cells via CD44 receptor-mediated endocytosis. HA/CS NPs selectiveness towards CD44 was highlighted by blocking CD44 receptor by anti-CD44 primary antibody and by comparison to CS-based NPs cellular uptake. Eventually, high effectiveness in inhibiting cell proliferation was demonstrated on-chip synthetized EVE loaded HA/CS NPs by tracking in vitro DNA synthesis. |
| first_indexed | 2024-04-13T06:11:59Z |
| format | Article |
| id | doaj.art-a24eb8ae14624833b2db20b3210b7c51 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-13T06:11:59Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-a24eb8ae14624833b2db20b3210b7c512022-12-22T02:59:00ZengMDPI AGPharmaceutics1999-49232020-03-0112326010.3390/pharmaceutics12030260pharmaceutics12030260On-Chip Synthesis of Hyaluronic Acid-Based Nanoparticles for Selective Inhibition of CD44+ Human Mesenchymal Stem Cell ProliferationEnrica Chiesa0Federica Riva1Rossella Dorati2Antonietta Greco3Stefania Ricci4Silvia Pisani5Maddalena Patrini6Tiziana Modena7Bice Conti8Ida Genta9Department Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia, ItalyDepartment of Public Health, Experimental and Forensic Medicine, Histology and Embryology Unit, University of Pavia, Via Forlanini 10, 27100 Pavia, ItalyDepartment Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia, ItalyDepartment Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia, ItalyDepartment of Public Health, Experimental and Forensic Medicine, Histology and Embryology Unit, University of Pavia, Via Forlanini 10, 27100 Pavia, ItalyImmunology and Transplantation Laboratory, Pediatric Hematology Oncology Unit, Department of Maternal and Children’s Health, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, ItalyDepartment of Physics, University of Pavia, Via Bassi 6, 27100 Pavia, ItalyDepartment Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia, ItalyDepartment Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia, ItalyDepartment Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia, ItalyIn this study, an innovative microfluidics-based method was developed for one-step synthesis of hyaluronic acid (HA)-based nanoparticles (NPs), by exploiting polyelectrolytic interactions between HA and chitosan (CS), in order to improve reliability, reproducibility and possible scale-up of the NPs preparation. The on-chip synthesis, using a staggered herringbone micromixer, allowed to produce HA/CS NPs with tailored-made size and suitable for both parenteral (117.50 ± 4.51 nm) and loco-regional (349.15 ± 38.09 nm) administration, mainly composed by HA (more than 85% wt) with high negative surface charge (< −20 mV). HA/CS NPs were successfully loaded with a challenging water-insoluble molecule, Everolimus (EVE), an FDA- and EMA-approved anticancer drug able to lead to cell cycle arrest, reduced angiogenesis and promotion of apoptosis. HA/CS NPs resulted to be massively internalized in CD44+ human mesenchymal stem cells via CD44 receptor-mediated endocytosis. HA/CS NPs selectiveness towards CD44 was highlighted by blocking CD44 receptor by anti-CD44 primary antibody and by comparison to CS-based NPs cellular uptake. Eventually, high effectiveness in inhibiting cell proliferation was demonstrated on-chip synthetized EVE loaded HA/CS NPs by tracking in vitro DNA synthesis.https://www.mdpi.com/1999-4923/12/3/260hyaluronic acid-based nanocarrierseverolimuschitosanmicrofluidicscd44 targetinghuman mesenchymal stem cells |
| spellingShingle | Enrica Chiesa Federica Riva Rossella Dorati Antonietta Greco Stefania Ricci Silvia Pisani Maddalena Patrini Tiziana Modena Bice Conti Ida Genta On-Chip Synthesis of Hyaluronic Acid-Based Nanoparticles for Selective Inhibition of CD44+ Human Mesenchymal Stem Cell Proliferation Pharmaceutics hyaluronic acid-based nanocarriers everolimus chitosan microfluidics cd44 targeting human mesenchymal stem cells |
| title | On-Chip Synthesis of Hyaluronic Acid-Based Nanoparticles for Selective Inhibition of CD44+ Human Mesenchymal Stem Cell Proliferation |
| title_full | On-Chip Synthesis of Hyaluronic Acid-Based Nanoparticles for Selective Inhibition of CD44+ Human Mesenchymal Stem Cell Proliferation |
| title_fullStr | On-Chip Synthesis of Hyaluronic Acid-Based Nanoparticles for Selective Inhibition of CD44+ Human Mesenchymal Stem Cell Proliferation |
| title_full_unstemmed | On-Chip Synthesis of Hyaluronic Acid-Based Nanoparticles for Selective Inhibition of CD44+ Human Mesenchymal Stem Cell Proliferation |
| title_short | On-Chip Synthesis of Hyaluronic Acid-Based Nanoparticles for Selective Inhibition of CD44+ Human Mesenchymal Stem Cell Proliferation |
| title_sort | on chip synthesis of hyaluronic acid based nanoparticles for selective inhibition of cd44 human mesenchymal stem cell proliferation |
| topic | hyaluronic acid-based nanocarriers everolimus chitosan microfluidics cd44 targeting human mesenchymal stem cells |
| url | https://www.mdpi.com/1999-4923/12/3/260 |
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