title: Controlled release of doxorubicin loaded within magnetic thermo-responsive nanocarriers under magnetic and thermal actuation in a microfluidic channel.
abstract: We report a procedure to grow thermo-responsive polymer shells at the surface of magnetic nanocarriers made of multiple iron oxide superparamagnetic nanoparticles embedded in poly(maleic anhydride-alt-1-ocatadecene) polymer nanobeads. Depending on the comonomers and on their relative composition, tunable phase transition temperatures in the range between 26 and 47 °C under physiological conditions could be achieved. Using a suitable microfluidic platform combining magnetic nanostructures and channels mimicking capillaries of the circulatory system, we demonstrate that thermo-responsive nanobeads are suitable for localized drug delivery with combined thermal and magnetic activation. Below the critical temperature nanobeads are stable in suspension, retain their cargo, and cannot be easily trapped by magnetic fields. Increasing the temperature above the critical temperature causes the aggregation of nanobeads, forming clusters with a magnetic moment high enough to permit their capture by suitable magnetic gradients in close proximity to the targeted zone. At the same time the polymer swelling activates drug release, with characteristic times on the order of one hour for flow rates of the same order as those of blood in capillaries.
authors.affiliation: Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy.
authors.forename: Manuel
authors.initials: M
authors.lastname: Pernia Leal
authors.forename: Andrea
authors.initials: A
authors.lastname: Torti
authors.forename: Andreas
authors.initials: A
authors.lastname: Riedinger
authors.forename: Rocco
authors.initials: R
authors.lastname: La Fleur
authors.forename: Daniela
authors.initials: D
authors.lastname: Petti
authors.forename: Roberto
authors.initials: R
authors.lastname: Cingolani
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bertacco
authors.forename: Teresa
authors.initials: T
authors.lastname: Pellegrino
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry*; D060328:Magnetic Phenomena; D008299:Maleic Anhydrides / Q000138:chemical synthesis / Q000737:chemistry; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D008958:Models, Molecular; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008299:Maleic Anhydrides; D011108:Polymers; C016683:polymaleic anhydride; C052970:poly-N-isopropylacrylamide; D004317:Doxorubicin