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Multilayered Polyurethane/Poly(vinyl alcohol) Nanofibrous Mats for Local Topotecan Delivery as a Potential Retinoblastoma Treatment

Local chemotherapy using polymer drug delivery systems has the potential to treat some cancers, including intraocular retinoblastoma, which is difficult to treat with systemically delivered drugs. Well-designed carriers can provide the required drug concentration at the target site over a prolonged...

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Detalles Bibliográficos
Autores principales: Hobzova, Radka, Sirc, Jakub, Shrestha, Kusum, Mudrova, Barbora, Bosakova, Zuzana, Slouf, Miroslav, Munzarova, Marcela, Hrabeta, Jan, Feglarova, Tereza, Cocarta, Ana-Irina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222511/
https://www.ncbi.nlm.nih.gov/pubmed/37242640
http://dx.doi.org/10.3390/pharmaceutics15051398
Descripción
Sumario:Local chemotherapy using polymer drug delivery systems has the potential to treat some cancers, including intraocular retinoblastoma, which is difficult to treat with systemically delivered drugs. Well-designed carriers can provide the required drug concentration at the target site over a prolonged time, reduce the overall drug dose needed, and suppress severe side effects. Herein, nanofibrous carriers of the anticancer agent topotecan (TPT) with a multilayered structure composed of a TPT-loaded inner layer of poly(vinyl alcohol) (PVA) and outer covering layers of polyurethane (PUR) are proposed. Scanning electron microscopy showed homogeneous incorporation of TPT into the PVA nanofibers. HPLC-FLD proved the good loading efficiency of TPT (≥85%) with a content of the pharmacologically active lactone TPT of more than 97%. In vitro release experiments demonstrated that the PUR cover layers effectively reduced the initial burst release of hydrophilic TPT. In a 3-round experiment with human retinoblastoma cells (Y-79), TPT showed prolonged release from the sandwich-structured nanofibers compared with that from a PVA monolayer, with significantly enhanced cytotoxic effects as a result of an increase in the PUR layer thickness. The presented PUR-PVA/TPT-PUR nanofibers appear to be promising carriers of active TPT lactone that could be useful for local cancer therapy.