title: Structural investigation and intracellular trafficking of a novel multicomposite cationic solid lipid nanoparticle platform as a pDNA carrier.
abstract: BACKGROUND
  The ability to efficiently cross cellular barriers and accomplish high-level transgene expression is a critical challenge to broad application of nonviral vectors, such as cationic solid lipid nanoparticles (SLN).
  
  
  OBJECTIVE
  This study aims to design and characterize in vitro multicomposite SLN as a novel platform for pDNA delivery.
  
  
  CONCLUSIONS
  The distribution of each component (stearic acid, stearylamine, phosphatidylcholine, cholesterol, protamine and Pluronic F68) in the SLN matrix was studied by electron spectroscopy for chemical analysis and NMR in order to establish its influence on SLN cytotoxicity and transfection efficiency. Multicomposite SLN mediated the expression of enhanced green fluorescent protein in a way comparable with the positive control, but inducing a lower cytotoxicity. Moreover, the carrier exhibited the ability to enter the nucleoli, probably as a result of the synergic action of the nuclear localization signal of protamine and the flexibility of the lipid matrix owing to the phosphatidylcholine.
  
  
  CONCLUSIONS
  The multicomposite SLN showed good transfection efficiency and negligible cytotoxicity, both crucial factors for an efficient gene-delivery system. Considering the fact that nucleoli have emerged in recent years as important targets in many fields, this novel carrier could have significant future therapy involvements whenever there is a requirement to overcome subcellular barriers. However, further work needs to be carried out in order to fully characterize the formulation, to elucidate where alternative colloidal structures might exist and play a role in obtaining the results presented.
authors: University of Modena and Reggio Emilia, Department of Pharmaceutical Sciences, Via Campi 183, 41125 Modena, Italy.
authors: Eleonora
authors: E
authors: Vighi
authors: Eliana
authors: E
authors: Leot
authors: Monica
authors: M
authors: Montanari
authors: Adele
authors: A
authors: Mucci
authors: Miriam
authors: M
authors: Hanuskova
authors: Valentina
authors: V
authors: Iannuccelli
mesh_terms: D000818:Animals; D019556:COS Cells; D002412:Cations; D002466:Cell Nucleolus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004247:DNA / Q000008:administration & dosage*; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D053758:Nanoparticles; D056951:Photoelectron Spectroscopy / Q000379:methods; D010957:Plasmids; D014162:Transfection
chemical_list: D002412:Cations; D008055:Lipids; D049452:Green Fluorescent Proteins; D004247:DNA