title: Hydrophobic lapatinib encapsulated dextran-chitosan nanoparticles using a toxic solvent free method: fabrication, release property & in vitro anti-cancer activity.
abstract: Dextran sulfate-chitosan (DS-CS) nanoparticles, which possesses properties such as nontoxicity, biocompatibility and biodegradability have been employed as drug carriers in cancer therapy. In this study, DS-CS nanoparticles were synthesized and their sizes were controlled by a modification of the divalent cations cross-linkers (Ca2+, Zn2+or Mg2+). Based on the optimized processing parameters, lapatinib encapsulated nanoparticles were developed and characterized by Dynamics Light Scattering (DLS) measurements, Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM). Calcium chloride (CaCl2) facilitated the formation of bare (100.3±0.80nm) and drug-loaded nanoparticles (134.3±1.3nm) with narrow size distributions being the best cross-linker. The surface potential of drug-loaded nanoparticles was -16.8±0.47mV and its entrapment and loading efficiency were 76.74±1.73% and 47.36±1.27%, respectively. Cellular internalization of nanoparticles was observed by fluorescence microscopy and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay was used to determine cytotoxicity of bare and drug-loaded nanoparticles in comparison to the free drug lapatinib. The MTT assay showed that drug-loaded nanoparticles had comparable anticancer activity to free drug within a duration of 48h. The aforementioned results showed that the DS-CS nanoparticles were able to entrap, protect and release the hydrophobic drug, lapatinib in a controlled pattern and could further serve as a suitable drug carrier for cancer therapy.
authors.affiliation: Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran; Center for Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 117576, Singapore.
authors.forename: Rezvan
authors.initials: R
authors.lastname: Mobasseri
authors.affiliation: Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Karimi
authors.affiliation: Center for Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 117576, Singapore. Electronic address: lingling_tian@nus.edu.sg.
authors.forename: Lingling
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran; Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: naderman@modares.ac.ir.
authors.forename: Hossein
authors.initials: H
authors.lastname: Naderi-Manesh
authors.affiliation: Center for Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 117576, Singapore; Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou 510632, China.
authors.forename: Seeram
authors.initials: S
authors.lastname: Ramakrishna
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D000067493:Dynamic Light Scattering; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D000077341:Lapatinib; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011799:Quinazolines / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D004337:Drug Carriers; D011799:Quinazolines; D000077341:Lapatinib; D048271:Chitosan
keywords: Anti-cancer; Box-Behnken matrix; Dextran sulfate; Drug delivery; Lapatinib; Nanoparticles