790 LIPOSOMES ASSISTED BLADDER UPTAKE OF NGF ANTISENSE OLIGONUCLEOTIDES AMELIORATE SYMPTOMS OF DETRUSOR OVERACTIVITY IN RAT MODEL (2011)

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research1 Apr 2011790 LIPOSOMES ASSISTED BLADDER UPTAKE OF NGF ANTISENSE OLIGONUCLEOTIDES AMELIORATE SYMPTOMS OF DETRUSOR OVERACTIVITY IN RAT MODEL Vikas Tyagi, MD Yoshio Sugino, MD Naoki Yoshimura, MD, PhD Michael Chancellor, and Pradeep TyagiPhD Vikas TyagiVikas Tyagi Royal Oak, MI More articles by this author , Yoshio SuginoYoshio Sugino Pittsburgh, PA More articles by this author , Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author , Michael ChancellorMichael Chancellor Royal Oak, MI More articles by this author , and Pradeep TyagiPradeep Tyagi Royal Oak, MI More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.608AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Sequence-specific gene-silencing mechanism is a promising approach to develop a new therapeutics. However, inefficient intracellular uptake of the oligonucleotides ODN is a major impediment. The aim of the study was to examine the feasibility of liposomes to improve bladder uptake of phosphorothioate ODN. METHODS Female Sprague-dawley rats anaesthetized with isoflurane were instilled 0.5 mL of either saline or liposomal fluorescent ODN (6 μM) for 30 min. Bladders were harvested at 8 and 24 h after instillation to visualize bladder uptake by fluorescence confocal microscopy. The efficacy of antisense treatments was assessed by cystometry and NGF immunohistochemistry. RESULTS The bright red fluorescence of TYE 563 attached to the instilled ODN revealed maximum bladder accumulation of ODN at 24 h. Baseline CMG under saline infusion 24 h after instillation was indistinct with mean intercontraction interval (ICI) of 18.44 ± 2.52 min and 18.29 ± 1.62 min in the vehicle and antisense treated groups, respectively. Rats instilled with saline or aqueous ODN without liposomes demonstrated AA induced bladder overactivity with ICI reduction of 49.71 ± 9.68% from baseline values compared to 14.17 ± 3.71% after instillation of liposomal ODN. Increased density of NGF immunostaining in urothelium of AA treated bladder sections was comparatively reduced in rats instilled with liposomal ODN. CONCLUSIONS Intravesical route can allow selective exposure of high concentration of antisense ODN to the NGF producing cells in urothelium and avoid systemic side effects from genetic manipulation of NGF expression and the safety concerns noted with systemic administration of monoclonal human NGF antibodies. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e318 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Vikas Tyagi Royal Oak, MI More articles by this author Yoshio Sugino Pittsburgh, PA More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Michael Chancellor Royal Oak, MI More articles by this author Pradeep Tyagi Royal Oak, MI More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...