title: Nitric oxide-releasing polymeric microspheres improve diabetes-related erectile dysfunction.
abstract: BACKGROUND
  We have used a long-acting nitric oxide (NO)-releasing polymer to develop injectable biodegradable microspheres capable of localized NO release over prolonged periods of time.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the therapeutic potential of these microspheres for diabetes-related erectile dysfunction (ED) in the rat model.
  
  
  METHODS
  NO-releasing microspheres were incubated in physiologic buffer, and in vitro NO release was measured using a Griess assay. To ensure no migration, microspheres were fluorescently tagged and injected into the corpus cavernosum of adult rats, and fluorescent imaging was performed weekly for 4 weeks, at which point rats were sacrificed. To assess physiologic efficacy, diabetes was induced in 40 rats using streptozotocin (STZ), whereas 10 rats were kept as age-matched controls. Diabetic rats were divided into four groups: no treatment, sildenafil, NO-releasing microspheres, and combination therapy. For each rat, the cavernosal nerve (CN) was stimulated at various voltages, and intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured via corpus cavernosum and carotid artery catheterization, respectively. Long-term efficacy was determined by injecting diabetic rats with microspheres and measuring erectile response at predetermined intervals for up to 5 weeks.
  
  
  METHODS
  Erectile response was determined via calculation of mean peak ICP/MAP and area under curve (AUC) for each experimental group.
  
  
  RESULTS
  Under physiologic conditions in vitro, microspheres continued NO release for up to 4 weeks. Fluorescent imaging revealed no detectable signal in tissues besides cavernosal tissue at 4 weeks postinjection. Upon CN stimulation, peak ICP/MAP ratio and AUC of diabetic rats improved significantly (P < 0.05) in microsphere and combination therapy groups compared with no treatment and sildenafil groups. In long-term efficacy studies, microspheres augmented the effect of sildenafil for 3 weeks following injection (P < 0.05).
  
  
  CONCLUSIONS
  NO-releasing microspheres significantly improved erectile response in diabetic rats for 3 weeks and hence offer a promising approach to ED therapy, either as monotherapy or combination therapy.
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA. samit.soni@bcm.edu
authors.forename: Samit D
authors.initials: SD
authors.lastname: Soni
authors.forename: Weitao
authors.initials: W
authors.lastname: Song
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: West
authors.forename: Mohit
authors.initials: M
authors.lastname: Khera
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology; D004359:Drug Therapy, Combination; D007172:Erectile Dysfunction / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008863:Microspheres; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D052250:Nitric Oxide Synthase Type III; D010410:Penile Erection / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use; D011687:Purines / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013311:Streptozocin; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D013311:Streptozocin; D000068677:Sildenafil Citrate; D052250:Nitric Oxide Synthase Type III
keywords: Corporal Smooth Muscle Relaxation; Diabetes; Erectile Dysfunction; Nitric Oxide; Rat; Therapy