title: A Microfluidic Platform to design crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for enhanced MRI.
abstract: Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T1is observed since a T1of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications.
authors.affiliation: Istituto Italiano di Tecnologia, IIT - Center for Advanced Biomaterials for Health Care, CABHC@CRIB, Largo Barsanti e Matteucci, 80125, Naples, Italy.|University of Naples Federico II, Department of Chemical Engineering, Materials and Industrial Production, P.le Tecchio 80, 80125, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Russo
authors.affiliation: Istituto Italiano di Tecnologia, IIT - Center for Advanced Biomaterials for Health Care, CABHC@CRIB, Largo Barsanti e Matteucci, 80125, Naples, Italy.|IRCCS Fondazione SDN, Istituto di Ricerca Diagnostica e Nucleare, 80143 Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bevilacqua
authors.affiliation: Istituto Italiano di Tecnologia, IIT - Center for Advanced Biomaterials for Health Care, CABHC@CRIB, Largo Barsanti e Matteucci, 80125, Naples, Italy.|University of Naples Federico II, Department of Chemical Engineering, Materials and Industrial Production, P.le Tecchio 80, 80125, Naples, Italy.|University of Naples Federico II, Department of Chemical Engineering, Materials and Industrial Production, P.le Tecchio 80, 80125, Naples, Italy.
authors.forename: Paolo Antonio
authors.initials: PA
authors.lastname: Netti
authors.affiliation: Istituto Italiano di Tecnologia, IIT - Center for Advanced Biomaterials for Health Care, CABHC@CRIB, Largo Barsanti e Matteucci, 80125, Naples, Italy.|University of Naples Federico II, Department of Chemical Engineering, Materials and Industrial Production, P.le Tecchio 80, 80125, Naples, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Torino
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry; D019786:Gadolinium DTPA / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods; D044085:Microfluidics / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry
chemical_list: D003287:Contrast Media; D006820:Hyaluronic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA