MP09-05 SILK-ELASTINLIKE POLYMERS ENHANCE THE ANTI-INFLAMMATORY AND ANALGESIC PROPERTIES OF SEMISYNTHETIC GLYCOSAMINOGLYCANS

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2018MP09-05 SILK-ELASTINLIKE POLYMERS ENHANCE THE ANTI-INFLAMMATORY AND ANALGESIC PROPERTIES OF SEMISYNTHETIC GLYCOSAMINOGLYCANS Mark Martin Jensen, Wanjian Jia, Austin Schults, Kyle Isaacson, Douglas Steinhauff, Bryant Green, Marcelo Correa, Jeremiah Alt, Joseph Cappello, Hamid Ghandehari, and Siam Oottamasathien Mark Martin JensenMark Martin Jensen More articles by this author , Wanjian JiaWanjian Jia More articles by this author , Austin SchultsAustin Schults More articles by this author , Kyle IsaacsonKyle Isaacson More articles by this author , Douglas SteinhauffDouglas Steinhauff More articles by this author , Bryant GreenBryant Green More articles by this author , Marcelo CorreaMarcelo Correa More articles by this author , Jeremiah AltJeremiah Alt More articles by this author , Joseph CappelloJoseph Cappello More articles by this author , Hamid GhandehariHamid Ghandehari More articles by this author , and Siam OottamasathienSiam Oottamasathien More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.331AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Rapid clearance, mucosal barriers, and tight epithelium create strong natural barriers within the bladder and bowel, reducing the efficacy of biologics and small molecule therapeutics. Silk-like and Elastin-like motifs were genetically recombined to create silk-elastinlike protein polymers (SELPs) that transition to solid matrices from injectable solutions in response to body temperature. Semi-synthetic glycosaminoglycan ethers (SAGEs) are a novel therapeutic class of polysaccharides that have both anti-inflammatory and analgesic properties. We hypothesized that SELP could be leveraged to overcome physiological barriers and enhance delivery and efficacy of water-soluble therapeutics, such as SAGE, to bladder and rectal tissues (see Figure 1). METHODS Material properties of SELP 815K, SELP 415K, Poloxamer 407 (PLX), and Poly(lactide-co-glycolide)-Poly(ethylene glycol)-Poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer based thermoresponsive delivery systems were evaluated using gelation time assays, rheology, scanning electron microscopy, in vivo delivery of fluorescently labeled SAGE, and enhancement of SAGE efficacy to ameliorate radiation-induced inflammation (RII) or LL-37 induced cystitis (IC) in murine models. Therapeutic efficacy was assessed using gross anatomical inspection, histology, ELISA for MPO activity, and other inflammatory markers, along with mechanical pain sensitization via Von Frey filament testing. RESULTS SELP 815K at 12% (w/w) solution in saline transitioned from an injectable fluidic solution to form a robust gel within 3 minutes after heating to 37 °C. SELP released SAGE over a 24 hr period in a controlled and tunable fashion. Both SELPs had lower injection viscosities but sill formed stronger gels compared to PLGA-PEG-PLGA and PLX. SELP enhanced the accumulation of SAGE in both rectal and bladder tissues and significantly improve the amelioration of pain and inflammatory responses in both models (P<0.001). CONCLUSIONS These results demonstrate the utility of SELP to enhance the delivery of SAGE within the rectum and bladder to improve treatment options for RII, IC, and other diseases afflicting the gastrointestinal and genitourinary systems. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e107 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Mark Martin Jensen More articles by this author Wanjian Jia More articles by this author Austin Schults More articles by this author Kyle Isaacson More articles by this author Douglas Steinhauff More articles by this author Bryant Green More articles by this author Marcelo Correa More articles by this author Jeremiah Alt More articles by this author Joseph Cappello More articles by this author Hamid Ghandehari More articles by this author Siam Oottamasathien More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...