4.7 Article

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

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PHARMACEUTICS
卷 15, 期 5, 页码 -

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MDPI
DOI: 10.3390/pharmaceutics15051398

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nanofibers; needleless electrospinning; multilayered structure; topotecan; prolonged release; retinoblastoma; cytotoxicity

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Local chemotherapy using polymer drug delivery systems has the potential to effectively treat cancers that are difficult to treat with systemically delivered drugs. This study proposes nanofibrous carriers composed of poly(vinyl alcohol) (PVA) and polyurethane (PUR) that can provide prolonged drug release and reduce side effects. The carriers demonstrated good loading efficiency and reduced initial burst release of the drug. In vitro experiments showed enhanced cytotoxic effects compared to a single-layer carrier, suggesting the potential for localized cancer therapy.
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.

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