Ruxolitinib-Loaded Imprinted Polymeric Drug Reservoir for the Local Management of Post-Surgical Residual Glioblastoma Cells
(1) Background: The current limitations of glioblastoma (GBM) chemotherapy were addressed by developing a molecularly imprinted polymer (MIP)-based drug reservoir designed for the localized and sustained release of ruxolitinib (RUX) within the tumor post-resection cavity, targeting residual infiltra...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/15/4/965 |
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| author | Alexandra-Iulia Bărăian Bogdan-Cezar Iacob Olga Sorițău Ioan Tomuță Lucia Ruxandra Tefas Lucian Barbu-Tudoran Sergiu Șușman Ede Bodoki |
| author_facet | Alexandra-Iulia Bărăian Bogdan-Cezar Iacob Olga Sorițău Ioan Tomuță Lucia Ruxandra Tefas Lucian Barbu-Tudoran Sergiu Șușman Ede Bodoki |
| author_sort | Alexandra-Iulia Bărăian |
| collection | DOAJ |
| description | (1) Background: The current limitations of glioblastoma (GBM) chemotherapy were addressed by developing a molecularly imprinted polymer (MIP)-based drug reservoir designed for the localized and sustained release of ruxolitinib (RUX) within the tumor post-resection cavity, targeting residual infiltrative cancerous cells, with minimum toxic effects toward normal tissue. (2) Methods: MIP reservoirs were synthesized by precipitation polymerization using acrylamide, trifluoromethacrylic acid, methacrylic acid, and styrene as monomers. Drug release profiles were evaluated by real-time and accelerated release studies in phosphate-buffered solution as a release medium. The cytotoxicity of polymers and free monomers was evaluated in vitro on GBM C6 cells using the Alamar Blue assay, optical microscopy, and CCK8 cell viability assay. (3) Results: Among the four synthesized MIPs, trifluoromethacrylic acid-based polymer (MIP 2) was superior in terms of loading capacity (69.9 μg RUX/mg MIP), drug release, and efficacy on GBM cells. Accelerated drug release studies showed that, after 96 h, MIP 2 released 42% of the loaded drug at pH = 7.4, with its kinetics fitted to the Korsmeyer–Peppas model. The cell viability assay proved that all studied imprinted polymers provided high efficacy on GBM cells. (4) Conclusions: Four different drug-loaded MIPs were developed and characterized within this study, with the purpose of obtaining a drug delivery system (DDS) embedded in a fibrin-based hydrogel for the local, post-surgical administration of RUX in GBM in animal models. MIP 2 emerged as superior to the others, making it more suitable and promising for further in vivo testing. |
| first_indexed | 2024-03-11T08:13:24Z |
| format | Article |
| id | doaj.art-020b06e9a902475a985380541aeefc10 |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-11T08:13:24Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-020b06e9a902475a985380541aeefc102023-11-16T22:52:19ZengMDPI AGPolymers2073-43602023-02-0115496510.3390/polym15040965Ruxolitinib-Loaded Imprinted Polymeric Drug Reservoir for the Local Management of Post-Surgical Residual Glioblastoma CellsAlexandra-Iulia Bărăian0Bogdan-Cezar Iacob1Olga Sorițău2Ioan Tomuță3Lucia Ruxandra Tefas4Lucian Barbu-Tudoran5Sergiu Șușman6Ede Bodoki7Department of Analytical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaDepartment of Analytical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaInstitute of Oncology “Prof. Dr. Ion Chiricuță”, Laboratory of Tumor Cell Biology and Radiobiology, 400015 Cluj-Napoca, RomaniaDepartment of Pharmaceutical Technology and Biopharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, RomaniaDepartment of Pharmaceutical Technology and Biopharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, RomaniaElectron Microscopy Center, Babes-Bolay University, 400006 Cluj-Napoca, RomaniaDepartment of Morphological Sciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, RomaniaDepartment of Analytical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania(1) Background: The current limitations of glioblastoma (GBM) chemotherapy were addressed by developing a molecularly imprinted polymer (MIP)-based drug reservoir designed for the localized and sustained release of ruxolitinib (RUX) within the tumor post-resection cavity, targeting residual infiltrative cancerous cells, with minimum toxic effects toward normal tissue. (2) Methods: MIP reservoirs were synthesized by precipitation polymerization using acrylamide, trifluoromethacrylic acid, methacrylic acid, and styrene as monomers. Drug release profiles were evaluated by real-time and accelerated release studies in phosphate-buffered solution as a release medium. The cytotoxicity of polymers and free monomers was evaluated in vitro on GBM C6 cells using the Alamar Blue assay, optical microscopy, and CCK8 cell viability assay. (3) Results: Among the four synthesized MIPs, trifluoromethacrylic acid-based polymer (MIP 2) was superior in terms of loading capacity (69.9 μg RUX/mg MIP), drug release, and efficacy on GBM cells. Accelerated drug release studies showed that, after 96 h, MIP 2 released 42% of the loaded drug at pH = 7.4, with its kinetics fitted to the Korsmeyer–Peppas model. The cell viability assay proved that all studied imprinted polymers provided high efficacy on GBM cells. (4) Conclusions: Four different drug-loaded MIPs were developed and characterized within this study, with the purpose of obtaining a drug delivery system (DDS) embedded in a fibrin-based hydrogel for the local, post-surgical administration of RUX in GBM in animal models. MIP 2 emerged as superior to the others, making it more suitable and promising for further in vivo testing.https://www.mdpi.com/2073-4360/15/4/965ruxolitinibglioblastomadrug reservoirmolecularly imprinted polymers |
| spellingShingle | Alexandra-Iulia Bărăian Bogdan-Cezar Iacob Olga Sorițău Ioan Tomuță Lucia Ruxandra Tefas Lucian Barbu-Tudoran Sergiu Șușman Ede Bodoki Ruxolitinib-Loaded Imprinted Polymeric Drug Reservoir for the Local Management of Post-Surgical Residual Glioblastoma Cells Polymers ruxolitinib glioblastoma drug reservoir molecularly imprinted polymers |
| title | Ruxolitinib-Loaded Imprinted Polymeric Drug Reservoir for the Local Management of Post-Surgical Residual Glioblastoma Cells |
| title_full | Ruxolitinib-Loaded Imprinted Polymeric Drug Reservoir for the Local Management of Post-Surgical Residual Glioblastoma Cells |
| title_fullStr | Ruxolitinib-Loaded Imprinted Polymeric Drug Reservoir for the Local Management of Post-Surgical Residual Glioblastoma Cells |
| title_full_unstemmed | Ruxolitinib-Loaded Imprinted Polymeric Drug Reservoir for the Local Management of Post-Surgical Residual Glioblastoma Cells |
| title_short | Ruxolitinib-Loaded Imprinted Polymeric Drug Reservoir for the Local Management of Post-Surgical Residual Glioblastoma Cells |
| title_sort | ruxolitinib loaded imprinted polymeric drug reservoir for the local management of post surgical residual glioblastoma cells |
| topic | ruxolitinib glioblastoma drug reservoir molecularly imprinted polymers |
| url | https://www.mdpi.com/2073-4360/15/4/965 |
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