Uptake of Etoposide in CT-26 Cells of Colorectal Cancer Using Folate Targeted Dextran Stearate Polymeric Micelles

Abstract

Targeted drug delivery using folate receptors is one of the most interesting chemotherapeutic research areas over the past few years. A novel folate targeted copolymer was synthesized using dextran stearate coupled to folic acid. FT-IR and NMR spectroscopy were used to confirm successful conjugation. Micelles prepared using this copolymer were characterized for their particle size, zeta potential, critical micelle concentration (CMC), drug loading capacity, and release efficiency. Cytotoxicity and cellular uptake of the micelles were estimated using CT-26 colorectal carcinoma cell line. FT-IR and NMR spectroscopy confirmed production of folate grafted dextran stearate copolymer. Low CMC value indicates that the copolymers are suitable for preparation of stable micelles useful in parenteral dosage forms. Particle size and zeta potential of the targeted nanoparticles were 105.5 ± 2.0 nm and −21.2 mV, respectively. IC50 of etoposide loaded in folate grafted dextran stearate enhanced about 20-fold compared to the pure drug (0.49 ± 0.11 μg/mL versus 9.41 ± 0.52 μg/mL). It seems that etoposide loaded in micelles of folate grafted dextran stearate copolymer is promising in reducing drug resistance of colorectal cancer by boosting etoposide cellular uptake.

Targeted Based Drug Delivery System for Colon Cancer

“…The NPs having the size around 100 to 200 nm gathered much efficiently in solid tumors than normal tissues. They also said that folate-targeted NPs might enter inside the tumor cells by endocytosis which is mediated through folate receptor [87]. They have seen that the addition of free folic acid to the folate-free culture medium of CT26 cells, cell viability was enhanced to 51.98 ± 6.3%.…”

Targeted delivery of etoposide to cancer cells by folate-modified nanostructured lipid drug delivery system

“…It could be explained that effective property of NLCs formula could facilitate greater cellular uptake than free drugs. The mechanism of action of ETP NLCs was proposed to be a cell uptake followed by a sustained drug release from the NLCs in combination with an intracellular P-gp inhibition ensuring a higher anticancer drug concentration inside the cancer cells (Varshosaz et al, 2014). Moreover, with the adding of the FA ligands, better cancer cell delivery effect of NLCs was observed than their non-modified ETP-NLCs counterparts.…”

“…It has been found that the half maximal inhibitory concentration (IC 50 ) of ETP using FA targeted dextran stearate polymeric micelles was 0.49 mg/ml for CT-26 cells while 9.41 mg/ml for the pure drug (Varshosaz et al, 2014). In a study on the antitumor activity, the uptake of FA-modified polymeric nanoparticles loaded with ETP by Hela cells and L929 cells was much higher than that of normal fibroblast cells (Kılıçay et al, 2011).…”

In VitroPET/MRI Diagnosis and Targeted Chemotherapy for Cancer Using Radiolabeled Nanoprobe : A Theragnostic Approach

“…One of the alternative approach is to use metal radionuclide including 68 Ga (t 1/2 = 68 min, β + = 89% and electron capture (EC) = 11%), which can be obtained easily from 68 Ge/ 68 Ga generator without the serve of cyclotron. 8 [20][21][22] .…”