title: Ocular delivery of pRNA nanoparticles: distribution and clearance after subconjunctival injection.
abstract: OBJECTIVE
  RNA nanoparticles derived from the three-way junction (3WJ) of the pRNA of bacteriophage phi29 DNA packaging motor were previously found to be thermodynamically stable. As the nanoparticles could have potential in ocular drug delivery, the objectives in the present study were to investigate the distribution of pRNA nanoparticles after subconjunctival injection and examine the feasibility to deliver the nanoparticles to the cells of cornea and retina.
  
  
  METHODS
  Alexa647-labeled pRNA nanoparticles (pRNA-3WJ and pRNA-X) and double-stranded RNA (dsRNA) were administered via subconjunctival injection in mice. Alexa647 dye was a control. Topical administration was performed for comparison. Ocular clearance of pRNA nanoparticles and dsRNA after the injection was assessed using whole-body fluorescence imaging of the eyes. The numbers of cells in the ocular tissues with nanoparticle cell internalization were determined in fluorescence microscopy of dissected eye tissues.
  
  
  RESULTS
  After subconjunctival injection, pRNA nanoparticles and dsRNA were observed to distribute into the eyes and cleared through the lymph. pRNA-3WJ, pRNA-X, and dsRNA were found in the cells of the conjunctiva, cornea, and sclera, but only pRNA-X was in the cells of the retina. Topical administration was not effective in delivering the nanoparticles to the eye.
  
  
  CONCLUSIONS
  The pRNA nanoparticles were delivered to the cells in the eye via subconjunctival injection, and cell internalization was achieved in the cornea with pRNA-3WJ and pRNA-X and in the retina with pRNA-X. Only the X-shape pRNA-X could enter the retina.
authors.affiliation: Division of Pharmaceutical Sciences James L. Winkle College of Pharmacy, University of Cincinnati, 3225 Eden Avenue 136 HPB, Cincinnati, Ohio, 45267, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.forename: S Kevin
authors.initials: SK
authors.lastname: Li
authors.forename: Hongshan
authors.initials: H
authors.lastname: Liu
authors.forename: Chia-Yang
authors.initials: CY
authors.lastname: Liu
authors.forename: Kathleen
authors.initials: K
authors.lastname: LaSance
authors.forename: Farzin
authors.initials: F
authors.lastname: Haque
authors.forename: Dan
authors.initials: D
authors.lastname: Shu
authors.forename: Peixuan
authors.initials: P
authors.lastname: Guo
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003228:Conjunctiva / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005123:Eye / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism; D012313:RNA / Q000008:administration & dosage* / Q000378:metabolism; D014764:Viral Proteins / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D014764:Viral Proteins; C040784:terminal protein, Bacillus phage phi29; D012313:RNA