Abbas Hemati Azandaryani1,2, Soheila Kashanian3,4, Katayoun Derakhshandeh5. 1. Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran. 2. Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. 3. Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran. Kashanian_s@yahoo.com. 4. Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Kashanian_s@yahoo.com. 5. Department of Pharmaceutics, Faculty of Pharmacy, Hamedan University of Medical Sciences, Hamedan, Iran.
Abstract
PURPOSE: Letrozole as a steroidal anticancer drug with hydrophobic nature is usually administrated by oral route for patient treatment and the injectable formulation for this drug has not still been reported. In this study, a new letrozole incorporated folate-conjugated polymer - lipid hybrid nanoparticles - is introduced for cancer treatment. METHODS: Nanoparticles were fabricated via modified oil in water ionic gelation method using optimization parameters and then were coupled to folic acid using carbodiimide activation. The physicochemical characterization in vitro drug release, cytotoxicity, and then ex vivo study of obtained carrier was investigated. RESULTS: Both thermal and crystallography studies proved the amorphous loading of drug in the nanocarrier. The cytotoxicity investigation with an average IC50 value of 79 ± 2.40 nM proved the efficiency of the coupled folic acid carrier for the intracellular uptake of letrozole on the breast cancer line. Ex vivo, the study proved the positive effect of the letrozole entrapment on the drug bioavailability. CONCLUSIONS: The obtained targeted nanocarrier could overcome the limitations associated with the LTZ as a potent non-steroidal drug. Both the entrapment and therapeutic efficiency of letrozole in the amphiphilic carrier were increased using the lipid nanoparticles and the surface modification, respectively.
PURPOSE:Letrozole as a steroidal anticancer drug with hydrophobic nature is usually administrated by oral route for patient treatment and the injectable formulation for this drug has not still been reported. In this study, a new letrozole incorporated folate-conjugated polymer - lipid hybrid nanoparticles - is introduced for cancer treatment. METHODS: Nanoparticles were fabricated via modified oil in water ionic gelation method using optimization parameters and then were coupled to folic acid using carbodiimide activation. The physicochemical characterization in vitro drug release, cytotoxicity, and then ex vivo study of obtained carrier was investigated. RESULTS: Both thermal and crystallography studies proved the amorphous loading of drug in the nanocarrier. The cytotoxicity investigation with an average IC50 value of 79 ± 2.40 nM proved the efficiency of the coupled folic acid carrier for the intracellular uptake of letrozole on the breast cancer line. Ex vivo, the study proved the positive effect of the letrozoleentrapment on the drug bioavailability. CONCLUSIONS: The obtained targeted nanocarrier could overcome the limitations associated with the LTZ as a potent non-steroidal drug. Both the entrapment and therapeutic efficiency of letrozole in the amphiphilic carrier were increased using the lipid nanoparticles and the surface modification, respectively.
Entities:
Keywords:
PLNs; ex vivo intestinal non-everted sac study; folic acid; letrozole; lipid; targeted drug delivery
Authors: Patrícia Severino; Samantha C Pinho; Eliana B Souto; Maria H A Santana Journal: Colloids Surf B Biointerfaces Date: 2011-04-12 Impact factor: 5.268