Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer
Abstract The paper presents the results of the experimental and analytical study of targeted drug-loaded polymer-based microspheres made from blend polymer of polylactic-co-glycolic acid and polycaprolactone (PLGA-PCL) for targeted and localized cancer drug delivery. In vitro sustained release with...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2023-08-01
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| Series: | Journal of Materials Science: Materials in Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s10856-023-06738-y |
| _version_ | 1797736406652551168 |
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| author | Chukwudalu C. Nwazojie John D. Obayemi Ali A. Salifu Sandra M. Borbor-Sawyer Vanessa O. Uzonwanne Chinyerem E. Onyekanne Udom M. Akpan Killian C. Onwudiwe Josephine C. Oparah Olushola S. Odusanya Winston O. Soboyejo |
| author_facet | Chukwudalu C. Nwazojie John D. Obayemi Ali A. Salifu Sandra M. Borbor-Sawyer Vanessa O. Uzonwanne Chinyerem E. Onyekanne Udom M. Akpan Killian C. Onwudiwe Josephine C. Oparah Olushola S. Odusanya Winston O. Soboyejo |
| author_sort | Chukwudalu C. Nwazojie |
| collection | DOAJ |
| description | Abstract The paper presents the results of the experimental and analytical study of targeted drug-loaded polymer-based microspheres made from blend polymer of polylactic-co-glycolic acid and polycaprolactone (PLGA-PCL) for targeted and localized cancer drug delivery. In vitro sustained release with detailed thermodynamically driven drug release kinetics, over a period of three months using encapsulated targeted drugs (prodigiosin-EphA2 or paclitaxel-EphA2) and control drugs [Prodigiosin (PGS), and paclitaxel (PTX)] were studied. Results from in vitro study showed a sustained and localized drug release that is well-characterized by non-Fickian Korsmeyer–Peppas kinetics model over the range of temperatures of 37 °C (body temperature), 41 °C, and 44 °C (hyperthermic temperatures). The in vitro alamar blue, and flow cytometry assays in the presence of the different drug-loaded polymer formulations resulted to cell death and cytotoxicity that was evidence through cell inhibition and late apoptosis on triple negative breast cancer (TNBC) cells (MDA-MB 231). In vivo studies carried out on groups of 4-week-old athymic nude mice that were induced with subcutaneous TNBC, showed that the localized release of the EphA2-conjugated drugs was effective in complete elimination of residual tumor after local surgical resection. Finally, ex vivo histopathological analysis carried out on the euthanized mice revealed no cytotoxicity and absence of breast cancer metastases in the liver, kidney, and lungs 12 weeks after treatment. The implications of the results are then discussed for the development of encapsulated EphA2-conjugated drugs formulation in the specific targeting, localized, and sustain drug release for the elimination of local recurred TNBC tumors after surgical resection. Graphical Abstract |
| first_indexed | 2024-03-12T13:13:21Z |
| format | Article |
| id | doaj.art-54ca8b52ec7f4005a2a55755096bb551 |
| institution | Directory Open Access Journal |
| issn | 1573-4838 |
| language | English |
| last_indexed | 2024-03-12T13:13:21Z |
| publishDate | 2023-08-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Materials Science: Materials in Medicine |
| spelling | doaj.art-54ca8b52ec7f4005a2a55755096bb5512023-08-27T11:08:00ZengSpringerJournal of Materials Science: Materials in Medicine1573-48382023-08-0134812410.1007/s10856-023-06738-yTargeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancerChukwudalu C. Nwazojie0John D. Obayemi1Ali A. Salifu2Sandra M. Borbor-Sawyer3Vanessa O. Uzonwanne4Chinyerem E. Onyekanne5Udom M. Akpan6Killian C. Onwudiwe7Josephine C. Oparah8Olushola S. Odusanya9Winston O. Soboyejo10Department of Materials Science and Engineering, African University of Science and TechnologyDepartment of Mechanical and Materials Engineering, Worcester Polytechnic InstituteDepartment of Mechanical and Materials Engineering, Worcester Polytechnic InstituteDepartment of Materials Science and Engineering, African University of Science and TechnologyDepartment of Mechanical and Materials Engineering, Worcester Polytechnic InstituteDepartment of Materials Science and Engineering, African University of Science and TechnologyDepartment of Materials Science and Engineering, African University of Science and TechnologyDepartment of Materials Science and Engineering, African University of Science and TechnologyDepartment of Materials Science and Engineering, African University of Science and TechnologyBiotechnology and Genetic Engineering Advanced Laboratory, Sheda Science and Technology Complex (SHESTCO)Department of Materials Science and Engineering, African University of Science and TechnologyAbstract The paper presents the results of the experimental and analytical study of targeted drug-loaded polymer-based microspheres made from blend polymer of polylactic-co-glycolic acid and polycaprolactone (PLGA-PCL) for targeted and localized cancer drug delivery. In vitro sustained release with detailed thermodynamically driven drug release kinetics, over a period of three months using encapsulated targeted drugs (prodigiosin-EphA2 or paclitaxel-EphA2) and control drugs [Prodigiosin (PGS), and paclitaxel (PTX)] were studied. Results from in vitro study showed a sustained and localized drug release that is well-characterized by non-Fickian Korsmeyer–Peppas kinetics model over the range of temperatures of 37 °C (body temperature), 41 °C, and 44 °C (hyperthermic temperatures). The in vitro alamar blue, and flow cytometry assays in the presence of the different drug-loaded polymer formulations resulted to cell death and cytotoxicity that was evidence through cell inhibition and late apoptosis on triple negative breast cancer (TNBC) cells (MDA-MB 231). In vivo studies carried out on groups of 4-week-old athymic nude mice that were induced with subcutaneous TNBC, showed that the localized release of the EphA2-conjugated drugs was effective in complete elimination of residual tumor after local surgical resection. Finally, ex vivo histopathological analysis carried out on the euthanized mice revealed no cytotoxicity and absence of breast cancer metastases in the liver, kidney, and lungs 12 weeks after treatment. The implications of the results are then discussed for the development of encapsulated EphA2-conjugated drugs formulation in the specific targeting, localized, and sustain drug release for the elimination of local recurred TNBC tumors after surgical resection. Graphical Abstracthttps://doi.org/10.1007/s10856-023-06738-yPLGA-PCL blendProdigiosinPaclitaxelEphA2MicrospheresTriple negative breast cancer |
| spellingShingle | Chukwudalu C. Nwazojie John D. Obayemi Ali A. Salifu Sandra M. Borbor-Sawyer Vanessa O. Uzonwanne Chinyerem E. Onyekanne Udom M. Akpan Killian C. Onwudiwe Josephine C. Oparah Olushola S. Odusanya Winston O. Soboyejo Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer Journal of Materials Science: Materials in Medicine PLGA-PCL blend Prodigiosin Paclitaxel EphA2 Microspheres Triple negative breast cancer |
| title | Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer |
| title_full | Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer |
| title_fullStr | Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer |
| title_full_unstemmed | Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer |
| title_short | Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer |
| title_sort | targeted drug loaded plga pcl microspheres for specific and localized treatment of triple negative breast cancer |
| topic | PLGA-PCL blend Prodigiosin Paclitaxel EphA2 Microspheres Triple negative breast cancer |
| url | https://doi.org/10.1007/s10856-023-06738-y |
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