title: Size-stable solid lipid nanoparticles loaded with Gd-DOTA for magnetic resonance imaging.
abstract: Solid lipid nanoparticles (SLNs) have recently emerged as nontoxic, versatile alternatives to traditional carriers (liposomes, polymeric nanoparticles) for drug delivery. Because SLNs are composed of a solid lipid core, they offer significant protection against chemical degradation of their drug cargo and offer the potential for controlled release. SLNs also hold promise for use as targeted agents and multimodal imaging agents. Here we report the synthesis and characterization of SLNs loaded with gadolinium (1,4,7,10-tetraazacyclododecane)-1,4,7,10-tetraacetate (Gd-DOTA) in order to produce a new category of stable T1-weighted (T1w) magnetic resonance imaging (MRI) contrast agents. Systematically varying components in the SLN synthesis, we demonstrated an increase in Gd-DOTA incorporation and an increase in longitudinal relaxivity (r1) through optimizing the amount of surfactant (Span 80) in the "oil" phase. These highly monodisperse SLNs confirm stable loading of Gd-DOTA and a stable size distribution (∼150 nm) over time in aqueous solution. Relaxivity measurements (1.4T, 37 °C) demonstrate that the r1 of Gd-DOTA does not strongly decrease following encapsulation in SLNs, demonstrating an advantage over liposomes. These Gd-loaded SLNs demonstrate enhanced contrast in vivo at 7T using T1w MRI and in the future can be loaded with other cargo (hydrophilic or hydrophobic) to enable functionality with other imaging modalities such as optical or positron emission tomography.
authors.affiliation: Department of Biomedical Engineering, University of California Davis , Davis, California 95616, United States.
authors.forename: Erica
authors.initials: E
authors.lastname: Andreozzi
authors.forename: Peter
authors.initials: P
authors.lastname: Wang
authors.forename: Anthony
authors.initials: A
authors.lastname: Valenzuela
authors.forename: Chuqiao
authors.initials: C
authors.lastname: Tu
authors.forename: Fredric
authors.initials: F
authors.lastname: Gorin
authors.forename: Marc
authors.initials: M
authors.lastname: Dhenain
authors.forename: Angelique
authors.initials: A
authors.lastname: Louie
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage* / Q000633:toxicity; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000633:toxicity; D008055:Lipids / Q000737:chemistry* / Q000633:toxicity; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000633:toxicity
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D008055:Lipids; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate