Tamoxifen-loaded folate-conjugate poly[(p-nitrophenyl acrylate)-co-(N-isopropylacrylamide)] sub-microgel as antitumoral drug delivery system.

J Biomed Mater Res A

Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.

Published: December 2010

Folate-conjugate poly[(p-nitrophenyl acrylate)-co-(N-isopropylacrylamide)] sub-microgel (F-SubMG) was loaded with tamoxifen (TMX) to obtain low (9.0 ± 0.4 μg TMX/mg F-SubMG) and high (112.0 ± 15.0 μg TMX/mg F-SubMG) load TMX-loaded F-SubMGs. Maximum in vitro drug release (77 ± 2% to 90 ± 2% of loaded TMX) took place between 47 and 168 h. The cytotoxicity of unloaded F-SubMGs in MCF-7 and HeLa cells was low; although it increased for high F-SubMG concentration. The administration of 10 μM TMX by TMX-loaded F-SubMGs was effective on both cellular types. Cell uptake of F-SubMGs took place in both cell types, but it was larger in HeLa cells because they are folate receptor positive. After subcutaneous administration (2.8 mg TMX/kg b.w.) in Wistar rats, F-SubMGs were detected at the site of injection under the skin, and a significant amount of them were included inside adipocytes. Signs of rejection were not observed after 60 days of injection. Pharmacokinetic study showed an increase in mean residence time of TMX and 4-hydroxytamoxifen (4-OHTMX), as well as a metabolite ratio (MR = AUC(4OHTMX) /AUC(TMX) ) nine times larger, when TMX was administered by drug-loaded F-SubMGs. Since 4-OHTMX is a more potent (at least 100-fold higher) antiestrogen than TMX, administration of TMX-loaded F-SubMGs can be considered an advantage.

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbm.a.32929DOI Listing

Publication Analysis

Top Keywords

tmx-loaded f-submgs
12
folate-conjugate poly[p-nitrophenyl
8
poly[p-nitrophenyl acrylate-co-n-isopropylacrylamide]
8
acrylate-co-n-isopropylacrylamide] sub-microgel
8
μg tmx/mg
8
tmx/mg f-submg
8
hela cells
8
f-submgs
7
tmx
6
tamoxifen-loaded folate-conjugate
4

Similar Publications

Tamoxifen-loaded folate-conjugate poly[(p-nitrophenyl acrylate)-co-(N-isopropylacrylamide)] sub-microgel as antitumoral drug delivery system.

J Biomed Mater Res A

December 2010

Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.

Folate-conjugate poly[(p-nitrophenyl acrylate)-co-(N-isopropylacrylamide)] sub-microgel (F-SubMG) was loaded with tamoxifen (TMX) to obtain low (9.0 ± 0.4 μg TMX/mg F-SubMG) and high (112.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!