Poly(d,l-lactide)/polyethylene glycol (PLA/PEG) micro/nanofibers loaded with paclitaxel (PTX, 10 wt%) were prepared by needless electrospinning technology, which allows large scale production for real medicinal practice. The fiber structure and properties were investigated by several methods including scanning electron microscopy, nitrogen adsorption/desorption isotherm measurements, differential scanning calorimetry, and X-ray diffraction measurements to examine their morphology (fiber diameter distribution, specific surface area, and total pore volume), composition, drug-loading efficiency, and physical state. An HPLC-UV method was optimized and validated to quantify in vitro PTX release into PBS. The results showed that the addition of PEG into PLA fibers promoted the release of higher amounts of hydrophobic PTX over prolonged time periods compared to fibers without PEG. An in vitro cell assay demonstrated the biocompatibility of PLA/PEG fibrous materials and showed significant cytotoxicity of PTX-loaded PLA/PEG fibers against a human fibrosarcoma HT1080 cell line. The chick chorioallantoic membrane assay proved that PTX-loaded fibers exhibited antiangiogenic activity, with a pronounced effect in the case of the PEG-containing fibers. In vivo evaluation of PTX-loaded PLA/PEG fibers in a human fibrosarcoma recurrence model showed statistically significant inhibition in tumor incidence and growth after primary tumor resection compared to other treatment groups.

Department of Analytical Chemistry Faculty of Science Charles University Hlavova 8 128 43 Prague 2 Czech Republic

Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University and Motol University Hospital 5 uvalu 84 150 06 Prague 5 Czech Republic

Department of Pharmaceutics and Biopharmaceutics University of Marburg Robert Koch Strasse 4 35037 Marburg Germany

Department of Physiology 3rd Faculty of Medicine Charles University Ruska 87 100 00 Prague 10 Czech Republic

Institute of Chemical Technology Technicka 5 166 28 Prague 6 Czech Republic

Institute of Macromolecular Chemistry Academy of Sciences of the Czech Republic Heyrovsky Sq 2 162 06 Prague 6 Czech Republic

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$a Poly(d,l-lactide)/polyethylene glycol micro/nanofiber mats as paclitaxel-eluting carriers: preparation and characterization of fibers, in vitro drug release, antiangiogenic activity and tumor recurrence prevention / $c R. Hobzova, Z. Hampejsova, T. Cerna, J. Hrabeta, K. Venclikova, J. Jedelska, U. Bakowsky, Z. Bosakova, M. Lhotka, S. Vaculin, M. Franek, M. Steinhart, J. Kovarova, J. Michalek, J. Sirc,

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$a Poly(d,l-lactide)/polyethylene glycol (PLA/PEG) micro/nanofibers loaded with paclitaxel (PTX, 10 wt%) were prepared by needless electrospinning technology, which allows large scale production for real medicinal practice. The fiber structure and properties were investigated by several methods including scanning electron microscopy, nitrogen adsorption/desorption isotherm measurements, differential scanning calorimetry, and X-ray diffraction measurements to examine their morphology (fiber diameter distribution, specific surface area, and total pore volume), composition, drug-loading efficiency, and physical state. An HPLC-UV method was optimized and validated to quantify in vitro PTX release into PBS. The results showed that the addition of PEG into PLA fibers promoted the release of higher amounts of hydrophobic PTX over prolonged time periods compared to fibers without PEG. An in vitro cell assay demonstrated the biocompatibility of PLA/PEG fibrous materials and showed significant cytotoxicity of PTX-loaded PLA/PEG fibers against a human fibrosarcoma HT1080 cell line. The chick chorioallantoic membrane assay proved that PTX-loaded fibers exhibited antiangiogenic activity, with a pronounced effect in the case of the PEG-containing fibers. In vivo evaluation of PTX-loaded PLA/PEG fibers in a human fibrosarcoma recurrence model showed statistically significant inhibition in tumor incidence and growth after primary tumor resection compared to other treatment groups.

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$a Hampejsova, Zuzana $u Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43 Prague 2, Czech Republic.

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$a Cerna, Tereza $u Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, V uvalu 84, 150 06 Prague 5, Czech Republic.

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$a Hrabeta, Jan $u Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, V uvalu 84, 150 06 Prague 5, Czech Republic.

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$a Venclikova, Kristyna $u Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic.

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$a Jedelska, Jarmila $u Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert Koch Strasse 4, 35037 Marburg, Germany.

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$a Bakowsky, Udo $u Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert Koch Strasse 4, 35037 Marburg, Germany.

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$a Bosakova, Zuzana $u Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43 Prague 2, Czech Republic.

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$a Vaculin, Simon $u Department of Physiology, 3rd Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague 10, Czech Republic.

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$a Franek, Miloslav $u Department of Physiology, 3rd Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague 10, Czech Republic.

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$a Steinhart, Milos $u Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic.

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$a Sirc, Jakub $u Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic. Electronic address: sirc@imc.cas.cz.

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