“OBEX” means “barrier” in Latin. UROBEX instillation is a method of introducing intravesical Elmiron® (pentosan polysulfate) into the bladders of patients with inflammation and degeneration of the urothelial lining using phospholid liposomes as nanocarriers. The goal of use is to restore the glycosaminoglycan layer of the bladder which is deficient in conditions such as interstitial cystitis, chemical cystitis, chronic cystitis, and radiation cystitis.
Interstitial Cystitis, also known as Interstitial Cystitis/ Bladder Pain Syndrome (IC/PBS) is a chronic severely debilitating painful condition due to inflammation of the tissues of the bladder wall. The cause is unknown. Symptoms include pelvic pain and pressure, urinary frequency, burning and urgency, and painful intercourse. IC/BPS is frequently misdiagnosed as a urinary tract infection. Patients often go years without a correct diagnosis. On average, there is about a 4-year delay between the time the first symptoms occur and the diagnosis is made. The condition is usually diagnosed by ruling out other conditions (such as sexually transmitted disease, bladder cancer, and bladder infections). Testing for IC/BPS is not always reliable. The KCl test, also known as the potassium sensitivity test, uses a mild potassium solution to test the integrity of the bladder wall. The condition generally occurs around age 30 to 50, although it has been reported in younger people. Women are 10 times more likely to have IC/BPS than men. Studies reveal that as many as 3 to 8 million Americans suffer from IC/BPS. The condition is associated with depression, emotional trauma, and other syndromes such as fibromyalgia, endometriosis, and irritable bowel syndrome. Advanced cases may reveal ulcers and erosions in the bladder lining with ultimate scarring and shrinkage of the bladder. The cause of IC/BPS is unknown. Theories have included neurologic, allergic, autoimmune, toxic exposure, genetic, abnormal mast cells, and psychological. It appears that most patients suffer from a deficiency of the protective glucosaminoglycan layer of the inner bladder lining (urothelium). This deficiency appears to be related to abnormal secretion of Heparin Binding Epidermal Growth Factor on a cellular level. The inadequate protective barrier results in increased permeability of the underlying submucosal tissues with subsequent bladder tissue destruction.
There is no known cure for interstitial cystitis, and there are no standard or consistently effective treatments. Treatment is based on trial and error but can include opioids, pain inhibitors, antidepressants, vistaril, detrussor relaxants, bladder hydrodistension, bladder instillations, biofeedback, dietary modification, and even surgery to enlarge or remove the bladder. Instillations are intravesical treatments performed with a number of different combination of “cocktails” that may include DMSO, steroids, heparin, chlorpactin, lidocaine, sodium hyaluronate (Cystistat), chondroitin (Uracyst), and sodium bicarbonate.
Elmiron (pentosan polysulfate) is the only medication taken by mouth that is specifically approved for treating IC. This medicine coats the bladder to help restore the glycosaminoglycan layer. There have been reported attempts in the literature at intravesical instillation of Elmiron also.
Interstitial cystitis and other forms of chronic bladder irritation (radiation, hemorrhagic, or bacterial) associated with loss of the protective urothelial lining may respond to intravesical glycosaminoglycan restorative therapy.
Pentosan Polysulfate in liposomes is now available as Urobex administered as an intravesical instillation. The concept of liposomal encapsulation is to protect and deliver the pentosan molecule to the damaged urothelium. Liposomes have the exact same composition as our cell walls and act as a drug carrier system that acts as a bio-adhesive for the pentosan which increases the bladder dwell time, bioavailability, and urothelial penetration. This temporary coating naturally reinforces the glycosaminoglycan GAG barrier, protecting the bladder wall and allowing healing to occur by interrupting a cycle of inflammation and degradation with overstimulation of afferent nerves. The pentosan in liposomes can be used alone or preferable in combination with cell therapy using stromal vascular fraction from our own adipose tissue.
In essence, liposomes act as a bio-adhesive that may make the GAG effective for days to weeks after a single instillation.
Pentosan Polysulfate (in the form of Elmiron) has been used safely for years as an instillation and liposomes (made out of phosphatidlycholine) are regarded as generally safe products and are commonly found in cosmetics and foods. This compound is not FDA approved and is patent pending. The compound is usually used as a weekly instillation and is available as “Pentosan in Liposomes” for use anywhere in the United States if your physician requests it from our compound pharmacy (Central Drugs in La Habra California. 562-691-6754). A pilot study to document efficacy is being conducted by Dr. Lander.
Learn More About Liposomes
Liposomes are simple microscopic vesicles in which an aqueous volume is entirely enclosed by a membrane composed of lipid molecule. The name liposome is derived from two Greek words: ‘Lipos’ meaning fat and ‘Soma’ meaning body. A liposome can be formed at a variety of sizes as unilamellar or multi-lamellar construction, and its name relates to its structural building blocks, phospholipids, and not to its size. Liposomes have emerged as useful carriers for in-vivo drug delivery.
Liposomes can be created by sonicating phospholipids in water. Liposomes or lipid based vesicles are microscopic (uni-lamellar or multi-lamellar) vesicles that are formed as a result of self-assembly of phospholipids in an aqueous media resulting in closed bi-layered structures. The assembly into closed bi-layered structures is a spontaneous process and usually needs some input of energy in the form of physical agitation, sonication, heat etc. Since a lipid bi-layered membrane encloses an aqueous core, both water and lipid soluble drugs can be successfully entrapped into the liposomes. The lipid soluble or lipophilic drugs get entrapped within the bi-layered membrane whereas water soluble or hydrophilic drugs get entrapped in the central aqueous core of the vesicles.
Advantage of Liposomes:
- Biocompatible, completely biodegradable, nontoxic, flexible, and non-immunogenic for systemic and non-systemic administrations.
- Can carry both water and lipid soluble drugs
- Can provide controlled and sustained release
- Stabilization of entrapped drug from hostile environment
- Help to reduce exposure of sensitive tissues to toxic drugs
- Drugs can be stabilized from oxidation
- Targeted drug delivery or site specific drug delivery
- Alter pharmacokinetics and pharmacodynamics of drugs
- Can incorporate micro and macro molecules
- Can be administered through various routes
- Act as a reservoir of drugs
- Can modulate the distribution of drug and increase therapeutic index
- Can modulate distribution of drugs
- Less stability and low solubility
- Problem to targeting various tissues due to their large size
- Short half life
- Occasionally, phospholipids undergo oxidation and hydrolysis like reaction
- Leakage and fusion of encapsulated drug or molecules
- High production cost
- Quick uptake by cells in reticulo-endothelial system
- Allergic reactions may occur to liposomal constituents.
Articles & Resources
- Dr. Lander’s data presented at 2013 Western Section American Urologic Meeting
- See Dr. Lander’s interview in the IC optimist Magazine
- The IC optimist Magazine Winter 2014
- Article: Liposomes: Novel Drug Delivery Carrier