title: Tunable hydrogel-nanoparticles release system for sustained combination therapies in the spinal cord.
abstract: Poly(methyl methacrylate) (PMMA) nanoparticles (NPs) were prepared by emulsion free radical polymerization. NPs with controlled dimension, as monitored by dynamic light scattering (DLS) and transmission electron microscopy (TEM), were produced by changing experimental parameters, such as the amount of emulsifier and the monomer feeding mode (batch or semi-batch). Then, different sized NPs (60, 80 and 130nm) were loaded in polysaccharide-polyacrylic acid based hydrogels, cross-linked by covalent ester bonds between polyacrylic acid (PAA) and agarose chains, with different pore sizes (30, 60, 90nm). The characteristics of the resulting composite hydrogel-NPs system were firstly studied in terms of rheological properties and ability to release Rhodamine B that presents steric hindrance similar to many neuroprotective agents used in spinal cord injury (SCI) repair. Then, diffusion-controlled release of different sized NPs from different entangled hydrogels was investigated in vitro and correlated with NPs diameter and hydrogel mean mesh size, showing different hindrances to the diffusion pathways. Release experiments and diffusion studies, rationalized by mathematical modeling and verified in vivo, allowed to build a material library able to satisfy different medical drug delivery needs.
authors.affiliation: Politecnico di Milano, Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta", via Mancinelli 7, 20131 Milano, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Rossi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferrari
authors.forename: Simonetta
authors.initials: S
authors.lastname: Papa
authors.forename: Davide
authors.initials: D
authors.lastname: Moscatelli
authors.forename: Tommaso
authors.initials: T
authors.lastname: Casalini
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Perale
authors.forename: Pietro
authors.initials: P
authors.lastname: Veglianese
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004655:Emulsions; D005609:Free Radicals / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry* / Q000493:pharmacokinetics; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D058105:Polymerization; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D012212:Rheology; D012235:Rhodamines / Q000493:pharmacokinetics; D012542:Scattering, Radiation; D013116:Spinal Cord / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005609:Free Radicals; D020100:Hydrogels; D012235:Rhodamines; D019904:Polymethyl Methacrylate; C029773:rhodamine B