icnmgrjill
06-26-2006, 09:38 AM
Dr. Jay Burstein (Dekalb Clinic, Dekalb IL) shares his thoughts on the research presented at this year's AUA conference.
INSTILLATION OF LIPOSOMES IS SUPERIOR TO DMSO OR PENTOSAN
POLYSULFATE IN REDUCING BLADDER HYPERACTIVITY
Vincent Hsieh*, Ratna Ganabathi, Naoki Yoshimura, Jonathan Kaufman, Michael B Chancellor, Pradeep Tyagi, Pittsburgh, PA
Introduction and Objective: To compare effect of intravesical liposomes (LPs), dimethyl sulfoxide (DMSO), and pentosan polysulfate (PPS) on a model of chemically-induced overactive bladder in the rat. Previously, our lab has demonstrated partial reversal of protamine sulfate (PS) and potassium chloride (KCL) -induced bladder hyperactivity by intravesical LP. The relative impact of LP versus other agents used in the clinic for treatment of IC is unknown.
Methods: Bladder reflex activity of female SD rats (250300g) was evaluated by continuous cystometry under urethane anesthesia (1.2g/kg). A transurethral bladder catheter (PE-50) connected by three-way stopcock to a pressure transducer and syringe pump used to record intravesical pressure. A control cystometrogram (CMG) was obtained by slow filling with normal saline (0.04mL/min) for 2h. Bladder hyperactivity was then induced by 1 hour infusion of PS (Sigma Chemical, 10 mg/mL) followed by a 1 hour infusion of KCl (500mM). Animals were then infused with KCl-based preparations containing either 50% DMSO (n=5), pentosan polysulfate (300mg in 50mL, n=5), or liposomes (Lipella Pharmaceutical, n=5) for 2h. The parameters measured included the intercontraction interval (ICI) and pressure threshold (PT) as well as baseline pressure (BP) which is representative of the post-contraction pressure nadir.
Results: After induction of hyperactive bladder, there was no significant difference in ICI, PT, or BP among groups. No statistically significant increase in ICI was observed with DMSO infusion. ICI was increased following infusion of PPS (109.3% increase, p<0.005) and LP (185.7% increase, p=0.005) (Figure 1). PT was not significantly affected by LP infusion but showed a small increase with PPS (12.4% increase, p<0.05). A large and significant increase in PT was elicited by DMSO (116.5% increase, p<0.005). BP was increased with DMSO (119.6%, p=0.005) but not with LP or PPS.
Conclusions: Intravesical instillation of DMSO did not have a beneficial effect in a PS/KCL bladder hyperactivity model while both PPS and liposome did with the intravesical liposome achieving nearly doubling of the intercontraction interval above PPS. Intravesical liposome may be considered a new therapy for interstitial cystitis.
COMMENT: This is an animal study that compared the effect of 3 different bladder instillation (irrigation) therapies on a model of chemically-induced overactive bladder in the rat. Dimethyl sulfoxide (DMSO), and pentosan polysulfate (Elmiron) are two well-known treatments that are FDA approved for IC. Liposomes are a novel approach to treat and deliver drugs. They are the lipid (fatty) portions of animal cell walls that form into a hollow sphere in the presence of a water solution. A liposome can be thought of as an empty ball of fat. Drugs can be inserted inside them and then used as a “drug delivery system”. In this study only “empty” liposomes were used and surprisingly had the most beneficial effect on bladder hyperactivity compared to Elmiron and DMSO.
INSTILLATION OF LIPOSOMES IS SUPERIOR TO DMSO OR PENTOSAN
POLYSULFATE IN REDUCING BLADDER HYPERACTIVITY
Vincent Hsieh*, Ratna Ganabathi, Naoki Yoshimura, Jonathan Kaufman, Michael B Chancellor, Pradeep Tyagi, Pittsburgh, PA
Introduction and Objective: To compare effect of intravesical liposomes (LPs), dimethyl sulfoxide (DMSO), and pentosan polysulfate (PPS) on a model of chemically-induced overactive bladder in the rat. Previously, our lab has demonstrated partial reversal of protamine sulfate (PS) and potassium chloride (KCL) -induced bladder hyperactivity by intravesical LP. The relative impact of LP versus other agents used in the clinic for treatment of IC is unknown.
Methods: Bladder reflex activity of female SD rats (250300g) was evaluated by continuous cystometry under urethane anesthesia (1.2g/kg). A transurethral bladder catheter (PE-50) connected by three-way stopcock to a pressure transducer and syringe pump used to record intravesical pressure. A control cystometrogram (CMG) was obtained by slow filling with normal saline (0.04mL/min) for 2h. Bladder hyperactivity was then induced by 1 hour infusion of PS (Sigma Chemical, 10 mg/mL) followed by a 1 hour infusion of KCl (500mM). Animals were then infused with KCl-based preparations containing either 50% DMSO (n=5), pentosan polysulfate (300mg in 50mL, n=5), or liposomes (Lipella Pharmaceutical, n=5) for 2h. The parameters measured included the intercontraction interval (ICI) and pressure threshold (PT) as well as baseline pressure (BP) which is representative of the post-contraction pressure nadir.
Results: After induction of hyperactive bladder, there was no significant difference in ICI, PT, or BP among groups. No statistically significant increase in ICI was observed with DMSO infusion. ICI was increased following infusion of PPS (109.3% increase, p<0.005) and LP (185.7% increase, p=0.005) (Figure 1). PT was not significantly affected by LP infusion but showed a small increase with PPS (12.4% increase, p<0.05). A large and significant increase in PT was elicited by DMSO (116.5% increase, p<0.005). BP was increased with DMSO (119.6%, p=0.005) but not with LP or PPS.
Conclusions: Intravesical instillation of DMSO did not have a beneficial effect in a PS/KCL bladder hyperactivity model while both PPS and liposome did with the intravesical liposome achieving nearly doubling of the intercontraction interval above PPS. Intravesical liposome may be considered a new therapy for interstitial cystitis.
COMMENT: This is an animal study that compared the effect of 3 different bladder instillation (irrigation) therapies on a model of chemically-induced overactive bladder in the rat. Dimethyl sulfoxide (DMSO), and pentosan polysulfate (Elmiron) are two well-known treatments that are FDA approved for IC. Liposomes are a novel approach to treat and deliver drugs. They are the lipid (fatty) portions of animal cell walls that form into a hollow sphere in the presence of a water solution. A liposome can be thought of as an empty ball of fat. Drugs can be inserted inside them and then used as a “drug delivery system”. In this study only “empty” liposomes were used and surprisingly had the most beneficial effect on bladder hyperactivity compared to Elmiron and DMSO.