title: Anatomical Targeting Improves Delivery of Unconjugated Nanoparticles to the Testicle.
abstract: OBJECTIVE
  Nanoparticles, which are submicroscopic particles typically ranging from 100 to 300 nm, are interesting as potential treatment of testicular disorders because they can be engineered to allow delivery to privileged tissues, such as across the blood-brain barrier or theoretically the blood-testis barrier. We compared the effects of anatomical and/or ligand targeting on testicular nanoparticle uptake in a rat model.
  
  
  METHODS
  A total of 48 rats were divided into 6 groups, including a control group and groups that received intra-arterial injection of unconjugated nanoparticles with and without saline flush, intravenous injection of unconjugated nanoparticles, intra-arterial injection of follicle stimulating hormone conjugated nanoparticles, intravenous injection of follicle stimulating hormone conjugated nanoparticles and intra-arterial injection of transactivating transcriptor conjugated nanoparticles. A dose response curve was assessed for intra-arterially injected unconjugated nanoparticles. Using high performance liquid chromatography and histological analysis we determined nanoparticle uptake by the testicle at 4 hours.
  
  
  RESULTS
  Intra-arterial injection resulted in a 5.8-fold increase in uptake compared to intravenous injection at 35 mg/kg of unconjugated nanoparticles (3.7 vs 0.6 μg nanoparticles per gm testicle, p = 0.04). Anatomical targeting failed to improve testicular uptake in FSH conjugated nanoparticles (intra-arterial vs intravenous injection 0.33 vs 0.38 μg FSH nanoparticles per gm testicular tissue, p = 0.73). On fluorescence microscopy nanoparticles were noted in the testicular interstitium and seminiferous tubules, and absent from the testicular vasculature.
  
  
  CONCLUSIONS
  Arterial injection for anatomical targeting of nanoparticles to the testis is feasible, improves unconjugated nanoparticle delivery to testicular tissue and enables nanoparticles to cross the gonadal vascular endothelium and the blood-testis barrier.
authors: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio; Department of Biomedical Engineering, Lerner Research Institute (VL), Cleveland Clinic, Cleveland, Ohio. Electronic address: devonsnow@gmail.com.
authors: Devon C
authors: DC
authors: Snow-Lisy
authors: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio; Department of Biomedical Engineering, Lerner Research Institute (VL), Cleveland Clinic, Cleveland, Ohio.
authors: Edmund S
authors: ES
authors: Sabanegh
authors: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio; Department of Biomedical Engineering, Lerner Research Institute (VL), Cleveland Clinic, Cleveland, Ohio.
authors: Mary K
authors: MK
authors: Samplaski
authors: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio; Department of Biomedical Engineering, Lerner Research Institute (VL), Cleveland Clinic, Cleveland, Ohio.
authors: Vinod
authors: V
authors: Labhasetwar
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis
chemical_list: D005640:Follicle Stimulating Hormone
keywords: blood-testis barrier; drug delivery systems; ligands; nanoparticles; testis