Author/Authors :
Shabani Ravari, Nazanin Nanotechnology Research Centre - Faculty of Pharmacy - Tehran University of Medical Sciences, Tehran , Goodarzi, Navid Nanotechnology Research Centre - Faculty of Pharmacy - Tehran University of Medical Sciences, Tehran , Alvandifar, Farhad Nanomedicine and Biomaterial Lab - Department of Pharmaceutics - Faculty of Pharmacy - Tehran University of Medical Sciences , Amini, Mohsen Department of Medicinal Chemistry - Faculty of Pharmacy - Tehran University of Medical Sciences, Tehran , Souri, Effat Department of Medicinal Chemistry - Faculty of Pharmacy - Tehran University of Medical Sciences, Tehran , Khoshayand, Mohammad Reza Department of Drug and Food Control - Faculty of Pharmacy and Pharmaceutical Quality Assurance Research Center - Tehran University of Medical Sciences , Hadavand Mirzaie, Zahra Nanomedicine and Biomaterial Lab - Department of Pharmaceutics - Faculty of Pharmacy - Tehran University of Medical Sciences , Atyabi, Fatemeh Nanotechnology Research Centre - Faculty of Pharmacy - Tehran University of Medical Sciences, Tehran - Nanomedicine and Biomaterial Lab - Department of Pharmaceutics - Faculty of Pharmacy - Tehran University of Medical Sciences , Dinarvand, Rassoul Nanotechnology Research Centre - Faculty of Pharmacy - Tehran University of Medical Sciences, Tehran - Nanomedicine and Biomaterial Lab - Department of Pharmaceutics - Faculty of Pharmacy - Tehran University of Medical Sciences
Abstract :
Background: Hyaluronic acid (HA) has been used for target-specific drug delivery because of strong affinity to CD44, a marker in which overexpressed in cancer cells and cancer stem cells. Conjugation of HA to the cytotoxic
agents via active targeting can improve efficacy, biodistribution, and water solubility. To be able to benefit from
passive targeting as well, a nanoparticulate system by counter ion using a polycation like chitosan may lead to a
perfect delivery system.
Methods: Water soluble Hyaluronic acid-Docetaxel (HA-DTX) conjugate was prepared and used to formulate
chitosan-coated HA-DTX nanoparticles by polyelectrolyte complex (PEC) method and optimized using Box-Behnken
design. Biological evaluation of nanoparticles was done in CD44+ cancer cells.
Results and discussion: Biological evaluation of optimized formula showed IC50 of nanoparticles for 4 T1 and
MCF-7 cell lines were 45.34 μM and 354.25 μM against 233.8 μM and 625.9 μM for DTX, respectively with increased
cellular uptake showed by inverted confocal microscope. Conclusion: Chitosan-coated HA-DTX nanoparticles were more effective against CD44+ cells than free DTX.
Keywords :
Glyconanoparticles , Nanomedicine , Polyelectrolye Complex , Macromolecular Drug Delivery , Polysaccharides
