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Polymers 2011, 3(3), 1107-1125; doi:10.3390/polym3031107

In Vitro and In Vivo Evaluation of a Folate-Targeted Copolymeric Submicrohydrogel Based on N-Isopropylacrylamide as 5-Fluorouracil Delivery System

1
Polymeric Materials Group for the Controlled Release of Bioactive Compounds in Biomedicine, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, 28040, Madrid, Spain
2
Polymeric Materials Group for the Controlled Release of Bioactive Compounds in Biomedicine, Escuela Universitaria de Enfermería, Fisioterapia y Podología, Universidad Complutense de Madrid, 28040, Madrid, Spain
3
Group of New Materials and Supramolecular Spectroscopy, Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco, Leioa, Spain
*
Author to whom correspondence should be addressed.
Received: 11 June 2011 / Accepted: 15 July 2011 / Published: 18 July 2011
(This article belongs to the Special Issue Polymer Nanogels and Microgels)
View Full-Text   |   Download PDF [387 KB, uploaded 18 July 2011]   |  

Abstract

Folate-targeted poly[(p-nitrophenyl acrylate)-co-(N-isopropylacrylamide)] nanohydrogel (F-SubMG) was loaded with 5-fluorouracil (5-FU) to obtain low (16.3 ± 1.9 μg 5-FU/mg F-SubMG) and high (46.8 ± 3.8 μg 5-FU/mg F-SubMG) load 5-FU-loaded F-SubMGs. The complete in vitro drug release took place in 8 h. The cytotoxicity of unloaded F-SubMGs in MCF7 and HeLa cells was low; although it increased for high F-SubMG concentration. The administration of 10 μM 5-FU by 5-FU-loaded F-SubMGs was effective on both cellular types. Cell uptake of F-SubMGs took place in both cell types, but it was higher in HeLa cells because they are folate receptor positive. After subcutaneous administration (28 mg 5-FU/kg b.w.) in Wistar rats, F-SubMGs were detected at the site of injection under the skin. Histological studies indicated that the F-SubMGs were surrounded by connective tissue, without any signs of rejections, even 60 days after injection. Pharmacokinetic study showed an increase in MRT (mean residence time) of 5-FU when the drug was administered by drug-loaded F-SubMGs. View Full-Text
Keywords: drug delivery; folate-conjugate nanogel; 5-fluorouracil; culture cells; pharmacokinetic drug delivery; folate-conjugate nanogel; 5-fluorouracil; culture cells; pharmacokinetic
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Blanco, M.D.; Guerrero, S.; Benito, M.; Fernández, A.; Teijón, C.; Olmo, R.; Katime, I.; Teijón, J.M. In Vitro and In Vivo Evaluation of a Folate-Targeted Copolymeric Submicrohydrogel Based on N-Isopropylacrylamide as 5-Fluorouracil Delivery System. Polymers 2011, 3, 1107-1125.

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