MP43-11 DEVELOPMENT OF A NANOSPHERE BASED DELIVERY OF SILDENAFIL TO SITES OF NERVE INJURY FOR PREVENTION OF POST-PROSTATECTOMY ERECTILE DYSFUNCTION USING A RAT MODEL OF CAVERNOUS NERVE INJURY

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research I1 Apr 2014MP43-11 DEVELOPMENT OF A NANOSPHERE BASED DELIVERY OF SILDENAFIL TO SITES OF NERVE INJURY FOR PREVENTION OF POST-PROSTATECTOMY ERECTILE DYSFUNCTION USING A RAT MODEL OF CAVERNOUS NERVE INJURY Neal Patel, Amirali Salmasi, Michael Dinizo, Ritu Goyal, Johanna Hannan, Geun Taek Lee, Joachim Kohn, Trinity J. Bivalacqua, and Isaac Yi Kim Neal PatelNeal Patel More articles by this author , Amirali SalmasiAmirali Salmasi More articles by this author , Michael DinizoMichael Dinizo More articles by this author , Ritu GoyalRitu Goyal More articles by this author , Johanna HannanJohanna Hannan More articles by this author , Geun Taek LeeGeun Taek Lee More articles by this author , Joachim KohnJoachim Kohn More articles by this author , Trinity J. BivalacquaTrinity J. Bivalacqua More articles by this author , and Isaac Yi KimIsaac Yi Kim More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1168AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Currently, there is no effective therapy to re-establish penile innervation and regenerate damaged cavernous nerves in post- radical prostatectomy (RP) patients. We propose to locally deliver sildenafil using nanosphere technology directly applied to injured cavernous nerves. The use of nanospheres (NSP) represents an innovative approach to increase the bioavailability, solubility, circulation time, and resistance to metabolic degradation of hydrophobic drugs, such as sildenafil. Methods Sildenafil loaded NSP which are tyrosine-derived copolymers that spontaneously self-assemble in aqueous media were produced. NSP provide an 80% dose delivery of a total of 50.7ng of sildenafil in the first 24 hours. Twenty four male Sprague Dawley rats were randomized into 4 groups. Three groups of rats received bilateral crush nerve injury (BCNI) and one group received no injury (sham, n=6). Of the rats that underwent BCNI, one group received no intervention (BNCI, n=6), while one group received sildenafil loaded NSP over site of induced crush injury bilaterally (BCNI+Sil+NSP, n=6), and the last group was treated with empty nanospheres after BCNI (NSP, n=6). After 14 days, each rat underwent erectile function testing and immunohistochemistry of neurofilament in the penile dorsal nerve was performed on mid penile cross-sections. Results Erectile function in rats treated with sildenafil loaded NSPs was significantly improved compared to the BNCI group (p<0.05). Neurofilament staining was significantly greater in sildenafil loaded NSP group compared to the BNCI group (p<0.05, Figure 1). Conclusions Immediate placement of a localized drug delivery system such as sildenafil loaded NSPs to the site of nerve injury showed improved erectile function, and neurofilament staining showed evidence of neuroprotection in the sildenafil loaded NSP treated group compared to the BNCI group. This therapeutic approach of localized drug delivery at the time of surgery would benefit a large number of post-RP patients and improve cavernous nerve regeneration. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e481 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Neal Patel More articles by this author Amirali Salmasi More articles by this author Michael Dinizo More articles by this author Ritu Goyal More articles by this author Johanna Hannan More articles by this author Geun Taek Lee More articles by this author Joachim Kohn More articles by this author Trinity J. Bivalacqua More articles by this author Isaac Yi Kim More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...