Currently one of the most effective FDA approved pharmacological treatments for Interstitial Cystitis/ Bladder Pain Syndrome (IC/PBS) is oral Pentosan Polysulfate PP (Elmiron®), a weak analog of heparin and one of the glycosaminoglycans. Although the Elmiron®, website states that the exact cause of action is unknown, it is commonly considered that the PP active agent is absorbed by the GI tract and secreted in the urine where it forms a coating which simulates the natural glycosaminoglycan layer resulting in a protective barrier. However, only 6% of the orally ingested product is secreted into the bladder and this is washed out relatively rapidly resulting in the need for dosing every 8 hours. Oral PP has been shown benefit over placebo in trials but can be associated with significant systemic side effects such as GI intolerance and hair loss (1,2,3). Nevertheless, favorable safety data for the use of intravesical or oral PP is quite extensive (4). Many clinicians will use PP as an intravesical instillation with literature and anecdotal support for improved efficacy using this delivery method (5).
Inefficient oral absorption and a hostile high proton environment with relatively rapid washout diminish the efficacy of barrier restoration therapy. In an effort to improve drug delivery, protect the glycosaminoglycan GAG molecule, prolong dwell times (from hours to weeks), and enable effective urothelial absorption, high quality multi-lamellar liposomes can be used to encapsulate the PP which can be used as an intravesical instillation therapy. Liposomes are phospholipid concentric bilayer nanospheres mimicking human cell walls. Liposomes can encapsulate other agents to protect them and then act as a bio-adhesive by forming a molecular film on the urothelium. Liposomes can adsorb onto cell surfaces and fuse with cells to allow drug delivery inside cell walls (6,7,8). There is evidence that empty liposomes alone can mitigate irritative bladder symptoms in comparison to placebo (9,10). Liposomes are common in foods and cosmetics and are generally regarded as safe (GRAS) products. “Obex” means “barrier” in Latin. Nanologix Research Inc produces UROBEX™ which contains Pentosan Polysulfate (PP) encapsulated in liposomes manufactured using proprietary technology that permits cost effective liposome production. This agent has been used under investigational
At the Western Section AUA in 2013, our research team presented our initial series of 8 patients with severe refractory IC who received instillations of Urobex™ every 2 weeks in an IRB study. No adverse events were recorded in this pilot study. Mean 3 month O’Leary-Sant index scores decreased from 26.5+/- 7.2 to 13.8+/- 9.6 and mean PUF scores decreased from 24.9+/- 14.3 to 12.1+/-9.6. Longer term follow up showed sustained improvement. We have seen no significant adverse side effects related to instillation of Urobex™ and results are promising with significant improvement in subjective outcomes testing.
Urobex™ uses a liposomal nanocarrier delivery system to protect PP from a hostile proton environment to increase dwell time and bio-adhesion. One instillation can provide relief for an extended time period and a series of instillations has provided long term relief from chronic debilitating symptoms in our patients. This represents an IC therapy that has potential for significantly improved efficacy over any other form of oral or intravesical GAG administration. Pre-clinical studies will soon be initiated to pursue an IND. Urobex™ technology is patented.
Western Section AUA 2013 Poster: INTRAVESICAL PENTOSAN POLYSULFATE ENCAPSULATED IN A LIPOSOME NANOCARRIER FOR INTERSTITIAL CYSTITIS. Elliot B. Lander MD, Jackie R. See MD
Paper submitted to American Journal of Clinical and Experimental Urology: INTRAVESICAL PENTOSAN POLYSULFATE IN LIPOSOMES FOR INTERSTITIAL CYSTITIS
Additional References: Waters MG1, Suleskey JF, Finkelstein LJ, Van Overbeke ME, Zizza VJ,
Stommel M. Interstitial cystitis: a retrospective analysis of treatment with pentosan polysulfate and follow-up patient survey. J Am Osteopath Assoc. 2000 Mar;100(3 Suppl):S13-8.  Hanno PM. Analysis of long-term Elmiron therapy for interstitial cystitis. Urology. 1997 May;49(5A Suppl):93-9.  Parsons CL, Mulholland SG. Successful therapy of interstitial cystitis with pentosan polysulfate. J Urol. 1987 Sep;138(3):513-6.  Anderson VR1, Perry CM Pentosan polysulfate: a review of its use in the relief of bladder pain or discomfort in interstitial cystitis. Drugs. 2006;66(6):821-35.  Davis EL1, El Khoudary SR, Talbott EO, Davis J, Regan LJ. Safety and efficacy of the use of intravesical and oral pentosan polysulfate sodium for interstitial cystitis: a randomized double-blind clinical trial. J Urol. 2008 Jan;179(1):177-85. Epub 2007 Nov 14.  Giannantoni A1, Di Stasi SM, Chancellor MB, Costantini E, Porena M. New frontiers in intravesical therapies and drug delivery. Eur Urol. 2006 Dec;50(6):1183-93; discussion 1193. Epub 2006 Aug 30.  Tyagi P1, Wu PC, Chancellor M, Yoshimura N, Huang L. Recent advances in intravesical drug/gene delivery. Mol Pharm. 2006 Jul-Aug;3(4):369-79.  Fraser MO1, Chuang YC, Tyagi P, Yokoyama T, Yoshimura N, Huang L, De Groat WC, Chancellor MB. Intravesical liposome administration–a novel treatment for hyperactive bladder in the rat. Urology. 2003 Mar;61(3):656-63.  Tyagi P1, Hsieh VC, Yoshimura N, Kaufman J, Chancellor MB Instillation of liposomes vs dimethyl sulphoxide or pentosan polysulphate for reducing bladder hyperactivity. BJU Int. 2009 Dec;104(11):1689-92. doi: 10.1111/j.1464-410X.2009.08673.x. Epub 2009 Jul 7.  Lee WC1, Chuang YC, Lee WC, Chiang PH. Safety and dose flexibility clinical evaluation of intravesical liposome in patients with interstitial cystitis or painful bladder syndrome. Kaohsiung J Med Sci. 2011 Oct;27(10):437-40. doi: 10.1016/j.kjms.2011.06.002. Epub 2011 Jul 23.