Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer.

Autor: Nwazojie CC; Department of Materials Science and Engineering, African University of Science and Technology, Km 10 Airport Road, Abuja, Nigeria.; Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA., Obayemi JD; Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA.; Department of Biomedical Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01605, USA., Salifu AA; Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA.; Department of Biomedical Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01605, USA.; Department of Engineering, Boston College, 140 Commonwealth Avenue, Chestnut Hill, USA., Borbor-Sawyer SM; Department of Materials Science and Engineering, African University of Science and Technology, Km 10 Airport Road, Abuja, Nigeria.; Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA.; Department of Biology, State University of New York, Buffalo State University, Buffalo, USA., Uzonwanne VO; Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA.; Department of Engineering, Boston College, 140 Commonwealth Avenue, Chestnut Hill, USA., Onyekanne CE; Department of Materials Science and Engineering, African University of Science and Technology, Km 10 Airport Road, Abuja, Nigeria.; Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA., Akpan UM; Department of Materials Science and Engineering, African University of Science and Technology, Km 10 Airport Road, Abuja, Nigeria.; Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA., Onwudiwe KC; Department of Materials Science and Engineering, African University of Science and Technology, Km 10 Airport Road, Abuja, Nigeria.; Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA., Oparah JC; Department of Materials Science and Engineering, African University of Science and Technology, Km 10 Airport Road, Abuja, Nigeria.; Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA., Odusanya OS; Biotechnology and Genetic Engineering Advanced Laboratory, Sheda Science and Technology Complex (SHESTCO), Abuja, Nigeria., Soboyejo WO; Department of Materials Science and Engineering, African University of Science and Technology, Km 10 Airport Road, Abuja, Nigeria. wsoboyejo@wpi.edu.; Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA. wsoboyejo@wpi.edu.; Department of Biomedical Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01605, USA. wsoboyejo@wpi.edu.
Jazyk: angličtina
Zdroj: Journal of materials science. Materials in medicine [J Mater Sci Mater Med] 2023 Aug 02; Vol. 34 (8), pp. 41. Date of Electronic Publication: 2023 Aug 02.
DOI: 10.1007/s10856-023-06738-y
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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