Intravesical instillation of pentosan polysulfate encapsulated in a liposome nanocarrier
for interstitial cystitis
Nanologix Research LLC
Am J Clin Exp Urol 2014;2(2):145-148www.ajceu.us /ISSN:2330-1910/AJCEU0000729
Elliot B Lander, Jackie R See
We determined the effect of intravesical instillation of pentosan polysulfate encapsulated in liposomes for refractory interstitial cystitis patients. This was an open label uncontrolled study. Subjects were recruited from a private urology practice. Inclusion criteria included patients who met NIDDK criteria for Interstitial Cystitis (IC) and who were responding poorly to conventional treatments. Exclusion criteria included evidence of a urinary tract infection, bladder cancer, or other forms of chronic cystitis. Patients received 400 mg of Pentosan Polysulfate (PP) encapsulated into liposomes as an intravesical instillation performed every 2 weeks for 3 months. Baseline and post treatment outcome measures were obtained that included the O’Leary-Sant Interstitial Cystitis Symptom and Problem Questionnaire and the Pelvic Pain and Urgency/Frequency Patient symptom Scale tests. A total of 37 instillations were used and no adverse events occurred. Clinically significant decreases in symptom scores greater than 50% were seen in virtually all outcome measures at 3 month follow up. All subjects reported remarkable subjective improvement in pain symptoms marked by decreased use of narcotics and increased enjoyment of daily activities. No patients developed systemic symptoms or poor tolerance of the instillations. Intravesical Pentosan Polysulfateencapsulated into liposomes can significantly decrease frequency, urgency, pain and improve quality of life for twomonths after deployment. Additional studies are needed to determine cellular effects of glycosaminoglycan restoration, ideal doses, dosing intervals, safety and cost-effectiveness of this therapy.
Given the small size of this study population (37treatments), it is difficult to draw conclusive evidence of safety and efficacy, however the PP/liposome compound appears to be effective in patients for whom no other treatment was helpful. Some of the patients had battled IC for 10 and 20 years and all were prior oral and or intravesical PP failures. In view of the dramatic symptom and bother score improvements, the compound certainly requires additional studies.
Outcomes are mitigated by the possibility of placebo effects and Hawthorne effects. It is notable that patients who received empty liposomes also reported some improvement in the literature . However, the fact that all patients were treatment failures with numerous other remedies and were advanced stage IC patients was compelling.
Urologists have instilled intravesical PP for decades with an excellent anecdotal and litera- ture safety record . Liposomes are common in foods and cosmetics and are generally regarded as safe (GRAS) products .
Further larger studies are indicated to establish safety of PP in liposomes. The addition of more subjects may reveal as yet unseen adverseeffects, decreased efficacy or reduced duration of effects. Long term efficacy is yet to bedetermined.
PP when delivered in liposomes is expected to be much more effective in delivering the active form of the molecule to the urothelial target. It is possible that other chronic inflammatory urothelial conditions such as chemical, hemorrhagic, and radiation cystitis may also be mitigated by PP/Liposome therapy.
This initial pilot study strongly supports thepotential efficacy and safety of intravesical PPencapsulated in small nanosphere liposomes used as a nanocarrier delivery system. Further safety and dosing studies are warranted. Liposomes protect small molecules like PP from a hostile proton environment to increase dwell time and bio-adhesion and potentiallyimprove efficacy over oral and intravesicalforms of GAG administration. Multicenter pla- cebo controlled studies will be required to establish the safety, dosing, and long termefficacy.