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

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 OPEN ACCESSPolymers 2011, 3 1108 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.

Activated Ester Containing Polymers: Opportunities and Challenges for the Design of Functional Macromolecules

“…441,442 The activated ester site allowed covalent conjugation of pyridine and folic-acid-functionalized amines for anticancer drug delivery. 443 In the recent past, reactive surface-immobilized hydrogels have attracted significant interest as biomimetic matrices to study the influence of different physiological signals (both chemical and mechanical) on the cell behavior. 444,445 These artificial matrices frequently rely on hydrogel films; their tunable swelling properties depend upon the extent of crosslinking.…”

Polyethylene Glycol Conjugated Polymeric Nanocapsules for Targeted Delivery of Quercetin to Folate-Expressing Cancer Cellsin Vitroandin Vivo

“…59 To our knowledge, no chemically modified FA-targeted PEGylated polymeric NCs with a coreÀshell structure has been prepared and tested previously. The closest to our system was described by Rata-Aguilar et al 60 in which FAÀchitosan conjugate was utilized to physically coat the preformed oilÀlecithin NCs with folic acid.…”

Folic Acid Decorated Chitosan Nanoparticles and its Derivatives for the Delivery of Drugs and Genes to Cancer Cells

“…As the HeLa cells are folate receptor-positive, the cellular uptake efficiency of F-SubMGs was higher in HeLa cells than MCF7 cells. These results demonstrate that the mean residence time of the drug was increased to 60 days and, therefore, the folate-conjugate submicrogels have great efficiency in controlling the release of 5-FU, which may lead to an innovative choice for treating numerous malignancies 54 .…”