ABSTRACT
OBJECTIVE AND AIM: Numerous clinical trials indicated combination regimens containing gemcitabine could extend progression-free survival of breast cancer patients without increasing the incidence of serious adverse effects. Orally administered gemcitabine is being metabolized by enzymes present in intestinal cells rapidly; thereupon, the current study was aimed to preparing, optimizing, and evaluating cytotoxicity of wheat germ agglutinin conjugated gemcitabine-chitosan nanoparticles (WGA-Gem-CNPs) in MCF-7 and HEK293 cells and to determining their cellular uptake by Caco-2 cells. METHODS: Gem-CNPs were prepared by Ionic Gelation method and optimum formulation was implied for WGA conjugation optimisation. Nanoparticles formation was approved by FTIR and DSC analyses; then particles were characterized by DLS and release profile was prepared. MTT assay was performed in MCF-7 and HEK293. RESULTS: Optimized Gem-CNPs and WGA-Gem-CNPs particle size were estimated as 126.6 ± 21.8 and 144.8 ± 36.1 nm, respectively. WGA conjugation efficacy was calculated as 50.98 ± 2.32 percent and encapsulation efficiency in WGA-Gem-CNPs was 69.44 ± 3.41 percent. Three-hour Caco-2 cellular uptake from Gem-CNPs and WGA-Gem-CNPs were estimated as averagely 3.5 and 4.5 folds higher than free drug, respectively. Gem-CNPs and WGA-Gem-CNPs reduced IC50 in MCF-7 cells by 2 and 2.5 folds, respectively; such decrease for HEK293 cells was as much as 2.4 and 6.3 folds, in same order. CONCLUSION: Demonstrated significant in vitro uptake of WGA-Gem-CNPs and cytotoxicity might be considered for more studies as a potential carrier for oral delivery of gemcitabine.
