title: Chitosan nanoparticles for lipophilic anticancer drug delivery: Development, characterization and in vitro studies on HT29 cancer cells.
abstract: The aim of this study was to develop chitosan-based nanoparticles that could encapsulate lipophilic molecules and deliver them to cancer cells. Nanoparticles were prepared with different molar ratios of chitosan, hyaluronic acid and sulphobutyl-ether-β-cyclodextrin and with or without curcumin. The nanosystems were characterized in terms of their size, zeta potential, morphology, encapsulation efficiency and stability in different media. Intestinal epithelial and colorectal cancer cells were treated with unloaded nanoparticles in order to study their effect on cellular membrane organization and ROS production. Finally, in vitro assays on both cellular lines were performed in order to evaluate the ability of nanoparticles to promote curcumin internalization and to study their effect on cell proliferation and cell cycle. Results show that nanoparticles were positively charged and their size increased with the increasing amounts of the anionic excipient. Nanoparticles showed good encapsulation efficiency and stability in water. Unloaded nanoparticles led to a change in lipid organization in the cellular membrane of both cell lines, without inducing ROS generation. Confocal microscopy, cell proliferation and cell cycle studies allowed the selection of the best formulation to limit curcumin cytotoxicity in normal intestinal epithelial cells and to reduce cancer cell proliferation. The latter was the result of the increase of expression for genes involved in apoptosis.
authors.affiliation: Department of Pharmacy and Biotechnologies, Alma Mater Studiorum, University of Bologna, Via San Donato 19/2, 40127 Bologna, Italy. Electronic address: angela.abruzzo2@unibo.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Abruzzo
authors.affiliation: Department of Pharmacy and Biotechnologies, Alma Mater Studiorum, University of Bologna INSTM, Centro S3 of CNR-Istituto Nanoscienze, Via Irnerio 48, 40126 Bologna, Italy. Electronic address: giampaolo.zuccheri@unibo.it.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Zuccheri
authors.affiliation: Department of Pharmacy and Biotechnologies, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. Electronic address: federica.bigucci@unibo.it.
authors.forename: Federica
authors.initials: F
authors.lastname: Belluti
authors.affiliation: Department of Pharmacy and Biotechnologies, Alma Mater Studiorum, University of Bologna, Via San Donato 19/2, 40127 Bologna, Italy. Electronic address: simona.provenzano@hotmail.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Provenzano
authors.affiliation: Department of Pharmacy and Biotechnologies, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy. Electronic address: laura.verardi2@unibo.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Verardi
authors.affiliation: Department of Pharmacy and Biotechnologies, Alma Mater Studiorum, University of Bologna, Via San Donato 19/2, 40127 Bologna, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Bigucci
authors.affiliation: Department of Pharmacy and Biotechnologies, Alma Mater Studiorum, University of Bologna, Via San Donato 19/2, 40127 Bologna, Italy. Electronic address: teresa.cerchiara2@unibo.it.
authors.forename: Teresa
authors.initials: T
authors.lastname: Cerchiara
authors.affiliation: Department of Pharmacy and Biotechnologies, Alma Mater Studiorum, University of Bologna, Via San Donato 19/2, 40127 Bologna, Italy. Electronic address: barbara.luppi@unibo.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Luppi
authors.affiliation: Department of Pharmacy and Biotechnologies, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy. Electronic address: natalia.calonghi@unibo.it.
authors.forename: Natalia
authors.initials: N
authors.lastname: Calonghi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003474:Curcumin / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D048271:Chitosan; D003474:Curcumin
keywords: Chitosan; Colorectal cancer cells; Confocal laser microscopy; Curcumin; Nanoparticles