title: Photocrosslinked poly(amidoamine) nanoparticles for central nervous system targeting.
abstract: This study presents an innovative method for the synthesis of polymeric nanoparticles (NPs) for central nervous system (CNS) targeting. The method is based on Ultraviolet light (UV)-induced crosslinking of diacrylamide-terminated oligomers of poly(amidoamine)s (PAAs), a widely used class of synthetic polymers in biomedical field research, especially in drug delivery thanks to their excellent biocompatibility and controlled biodegradability. Previous attempts aiming at preparing PAA-based NPs by self-assembly were challenged by lack of structural stability and consequently their early degradation and premature drug release. Here, the UV-induced crosslinked PAA NPs demonstrated to overcome main disadvantages of the self-assembled ones, as they showed improved stability and controlled release properties. Besides the remarkable efficiency to produce monodisperse and stable PAA NPs, the UV-induced crosslinking method is featured by great versatility and low environmental impact, since it does not require use of organic solvents and multiple purification steps. The capability of PAA NPs to encapsulate a fluorescently labelled model protein was experimentally demonstrated in this study. Cell culture experiments showed that PAA NPs were biocompatible and highly permeable across an in vitro blood-brain barrier model, thus highlighting their great potential as drug delivery vectors for CNS delivery.
authors.affiliation: SEMM, European School of Molecular Medicine, Via Adamello 16(,) 20139 Milan, Italy; Fondazione Filarete, Viale Ortles 22/4, 20139 Milan, Italy. Electronic address: smbatgv@gmail.com.
authors.forename: Smbat
authors.initials: S
authors.lastname: Gevorgyan
authors.affiliation: SEMM, European School of Molecular Medicine, Via Adamello 16(,) 20139 Milan, Italy; Fondazione Filarete, Viale Ortles 22/4, 20139 Milan, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Rossi
authors.affiliation: SEMM, European School of Molecular Medicine, Via Adamello 16(,) 20139 Milan, Italy; Fondazione Filarete, Viale Ortles 22/4, 20139 Milan, Italy.
authors.forename: Martino Alfredo
authors.initials: MA
authors.lastname: Cappelluti
authors.affiliation: SEMM, European School of Molecular Medicine, Via Adamello 16(,) 20139 Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tocchio
authors.affiliation: Fondazione Filarete, Viale Ortles 22/4, 20139 Milan, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Martello
authors.affiliation: Fondazione Filarete, Viale Ortles 22/4, 20139 Milan, Italy.
authors.forename: Irini
authors.initials: I
authors.lastname: Gerges
authors.affiliation: Fondazione Filarete, Viale Ortles 22/4, 20139 Milan, Italy; CIMaINa, Dipartimento di Fisica, Università degli Studi di Milano, Via Celoria 16, 20133 Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lenardi
authors.affiliation: Fondazione Filarete, Viale Ortles 22/4, 20139 Milan, Italy; CIMaINa, Dipartimento di Fisica, Università degli Studi di Milano, Via Celoria 16, 20133 Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Milani
authors.affiliation: Fondazione Filarete, Viale Ortles 22/4, 20139 Milan, Italy. Electronic address: simona.argentiere@fondazionefilarete.com.
authors.forename: Simona
authors.initials: S
authors.lastname: Argentiere
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D002232:Carbocyanines / Q000737:chemistry; D002490:Central Nervous System / Q000187:drug effects*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008027:Light; D051379:Mice; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D010539:Permeability; D010777:Photochemistry / Q000379:methods*; D011073:Polyamines / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012542:Scattering, Radiation; D012709:Serum Albumin / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D014466:Ultraviolet Rays
chemical_list: D001672:Biocompatible Materials; D002232:Carbocyanines; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D007074:Immunoglobulin G; C531249:Poly(amidoamine); D011073:Polyamines; D011108:Polymers; D012709:Serum Albumin; D012997:Solvents; C089187:cyanine dye 3