SBIR-STTR Award

Lipella Pharmaceutical Inc has been successful with development of intravesical liposome for painful bladder syndrome/Interstitial cystitis (PBS/IC). Through SBIR funding, Lipella has been successful in establishing the pre-clinical safety of its primary liposome formulation LPA-08. LPA-08 was discovered at the University of Pittsburgh and exclusively licensed to Lipella. IP of LPA-08 is protected through the filing of two full patent applications. A first patent has already been issued by the USPTO titled Application of Lipid Vehicles and Use for Drug Delivery, patent number 7,063,860, awarded June 20, 2006. This is totally new SBIR-I submission. Lipella will explore the pipeline potential of using intravesical liposome as an advanced intravesical drug delivery platform. Dr. Michael Chancellor was recently recruited from the University of Pittsburgh to become Director of Neurourology Program in the Department of Urology at William Beaumont Hospital in Royal Oak, MI. Dr. Chancellor is also Chairperson of the Scientific Advisory Board (SAB) at Lipella. In this SBIR-I, we will evaluate the 2nd major strength of intravesical liposome as a platform for intravesical drug delivery. This is a new topic for Lipella and is critical for Lipella to be a successful biotechnology company with a product development pipeline. In this six month pilot SBIR-I study, we will evaluate proof of concept of using liquid liposome delivery of botulinum toxin-A (Liposome-BoNT) into the bladder without need for cystscopic guided needle injection for refractory overactive bladder (OAB). If successful, we will leverage commercial investment and SBIR-II on further expanding liposome-BoNT for refractory OAB modeling, delivery of other drugs for OAB and PBS/IC, antibiotics for urinary tract infections and also liposome of chemotherapeutic, and/or immunomodulatory agents for treatment of localized bladder cancer.

Public Health Relevance:
Through previous SBIR-I funding, Lipella Pharmaceutical Inc has been successful in establishing the pre-clinical safety of its primary liposome formulation LPA-08. In this completely new SBIR-I submission. Lipella will explore the pipeline potential of using in- travesical liposome as an advanced intravesical drug delivery platform. In this six month pilot SBIR-I study, we will evaluate proof of concept of using liquid liposome delivery of botulinum toxin-A (Liposome-BoNT) into the bladder without need for cystscopic guided needle injection for refractory overactive bladder (OAB).

Public Health Relevance Statement:
Principal Investigator/Program Director (Last, First, Middle): Kaufman, Jonathan H Project Narrative Through previous SBIR-I funding, Lipella Pharmaceutical Inc has been successful in establishing the pre-clinical safety of its primary liposome formulation LPA-08. In this completely new SBIR-I submission. Lipella will explore the pipeline potential of using in- travesical liposome as an advanced intravesical drug delivery platform. In this six month pilot SBIR-I study, we will evaluate proof of concept of using liquid liposome delivery of botulinum toxin-A (Liposome-BoNT) into the bladder without need for cystscopic guided needle injection for refractory overactive bladder (OAB).

Project Terms:
Absorption; Active Follow-up; Adverse effects; Affect; American; Animals; Antibiotic Agents; Antibiotic Drugs; Antibiotics; Award; Biliary or Urinary Stones; Biological; Biotechnology; Bladder; Bladder Control; Bladder Diseases; Bladder Disorder; Bladder Dysfunction; Bladder Transitional Cell Epithelium; Bladder Urothelium; Bladder, Overactive; Body Tissues; Bontoxilysin; Botulin; Botulinum A Toxin; Botulinum Neurotoxin A; Botulinum Toxin Type A; Botulinum Toxins; Businesses; Calculi; Cancer of Bladder; Cancer of Urinary Bladder; Cathetergram; Catheterization; Cells; Chair; Chairman; Chairperson; Chairwoman; Clostridium Botulinum Toxin Type A; Clostridium botulinum A Toxin; Clostridium botulinum Toxins; Common Rat Strains; Communities; Conceptions; Core Facility; Cystoscopes; Development; Development and Research; Dose; Drug Delivery; Drug Delivery Systems; Drug Formulations; Drug Targeting; Drug Targetings; Drugs; Entire detrusor muscle of urinary bladder; Environment; Esteroproteases; Expenditure; Formulation; Formulations, Drug; Funding; Future; Goals; Grant; HOSP; Health; Hospitals; Human Figure; Human body; Image; Increased frequency of micturition; Injection of therapeutic agent; Injections; Injections, Intravesical; Instillations, Bladder; Intellectual Property; International; Interstitial Cystitis; Intravesical Injections; Intravesical Instillation; Investments; Laboratories; Legal patent; Licensing; Lipids; Liposomal; Liposomes; Liquid substance; Malignant Bladder Neoplasm; Malignant Tumor of the Bladder; Malignant neoplasm of urinary bladder; Mammals, Rats; Marketing; Medication; Medulla Spinalis; Membrane; Methods and Techniques; Methods, Other; Michigan; Micturition Reflex; Miscellaneous Antibiotic; Modeling; NIH; Nanoscale Science; Nanotechnology; National Institutes of Health; National Institutes of Health (U.S.); Needles; Oral; Overactive Bladder; Patents; Patients; Penetration; Peptidases; Peptide Hydrolases; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Preparations; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Principal Investigator; Process of absorption; Programs (PT); Programs [Publication Type]; Proteases; Proteinases; Proteolytic Enzymes; R & D; R&D; Rat; Rattus; Recruitment Activity; Refractory; Research; Research Institute; Residual volume; Rights; Risk; SBIR; SBIRS (R43/44); Safety; Small Business Innovation Research; Small Business Innovation Research Grant; Solutions; Spinal Cord; Staging; Stone; Taxes; Techniques; Therapeutic; Time; Tissues; Toxic effect; Toxicities; Treatment Side Effects; UTI; United States National Institutes of Health; Universities; Urinary Bladder Malignant Tumor; Urinary Frequency; Urinary Retention; Urinary System, Bladder; Urinary System, Urine; Urinary tract infection; Urinary tract infectious disease; Urine; Urology; Urothelium; absorption; afferent nerve; authority; bladder continence; botulinum neurotoxin; detrusor muscle; drug/agent; fluid; follow-up; imaging; improved; intravesical; liquid; lower urinary tract symptoms; membrane structure; micturition control; nano scale Science; nano tech; nano technology; nanotech; neurotransmitter release; painful bladder syndrome; pre-clinical; preclinical; product development; programs; public health relevance; recruit; research and development; research facility; response; sensory nerve; side effect; therapy adverse effect; trafficking; treatment adverse effect; uptake; urinary bladder; urinary bladder disorder; urinary continence; urinary control; urination control; voiding reflex

Lipella Pharmaceuticals Inc. has been funded by National Institutes of Health Small Business Innovation and Research (SBIR) grants to develop intravesical liposome nanoparticles to treat overactive bladder (OAB), interstitial cystitis/painful bladder syndrome (IC/PBS). The current SBIR will allow Lipella to expand its portfolio of patent applications regarding specific intravesical liposomal delivery techniques using liposomes as platform technology. In recent years, intravesical injections of botulinum neurotoxin (BoNT) have revolutionized the treatment of intractable lower urinary tract symptoms associated with idiopathic OAB or neurogenic detrusor overactivity. However, BoNT treatment is attended by many adverse effects such as impaired detrusor contractility, large post-void residual volumes and urinary retention. We hypothesize that adverse effects of BoNT can be drastically reduced by restricting its action only to urothelium and suburothelium space. We can achieve the objective of topical delivery of BoNT to bladder urothelium by using liposomal nanotechnology. The phase 1 funding for this project supported the laboratory scale development towards a liposome based liquid instillation of BoNT with significant physiological effect in bladder without any adverse effects on bladder histology. The studies described in phase II will test the hypothesis that liposome encapsulation provides higher therapeutic efficacy and safety (improves therapeutic index) than the currently used method of cystoscopic injection of BoNT. In addition, we will optimize the liposome platform technology for BoNT in comparison to a small molecular weight potent drug (tacrolimus) to achieve desired product stability of liposome formulation and shelf life that can sustain commercial use. Funding of this SBIR-II will allow Lipella to bridge our technology to additional intravesical drug delivery applications and will allow Lipella Pharmaceutical to prepare IND package for regulatory submission. Lipella has come a long way since the initial discovery and translation from academic to biotech startup. With the challenging economy condition and reduction in early-stage biotech venture capital funding, the importance of this SBIR-II to Lipella's future cannot be understated and it fulfills the important mission of NIH on bringing research discoveries from lab to the clinic. With the support of the NIH, Lipella can become a sustainable tax paying company that improves the health care of Americans and supports the local and national economy.

Public Health Relevance:
Lipella Pharmaceuticals Inc. has been funded by National Institutes of Health Small Business Innovation and Research (SBIR) grants to develop intravesical liposome and is now expanding its portfolio to intravesical liposomal drug delivery techniques. The development of a safe and effective liposomal liquid delivery of drugs into the bladder, without the need for endoscopic intervention and minimal risk of systemic toxicity, urinary irritation or retention is a priority. Drug delivery to block bladder inflammation will be an objective of this project and the successful completion of this grant will allow Lipella Pharmaceuticals to prepare a regulatory submission of liposomal based drug delivery IND.

Thesaurus Terms:
Adverse Effects;Affect;American;Biochemistry;Biological Chemistry;Biophysics;Biotechnology;Bladder;Bladder Transitional Cell Epithelium;Bladder Urinary System;Bladder Urothelium;Bontoxilysin;Businesses;Capital Financing;Capital Funding;Cathetergram;Catheterization;Chemotactic Cytokines;Clinic;Collaborations;Common Rat Strains;Cystoscopes;Data;Development;Doctor Of Philosophy;Drug Delivery;Drug Delivery Systems;Drug Formulations;Drug Targeting;Drugs;Formulation;Funding;Future;Grant;Healthcare;Histology;Homologous Chemotactic Cytokines;Inflammation;Injection Of Therapeutic Agent;Injections;Intercrines;Interstitial Cystitis;Intervention;Intervention Strategies;Intravesical Injections;Laboratories;Legal Patent;Licensing;Life;Liposomal;Liposomes;Liquid Substance;Marketing;Medication;Methods;Mission;Molecular;Molecular Weight;Nih;Nanoscale Science;Nanotechnology;National Institutes Of Health;Nerve Endings;Overactive Bladder;Patents;Patients;Pennsylvania;Ph.D.;Phd;Pharmaceutic Preparations;Pharmaceutical Agent;Pharmaceutical Preparations;Pharmaceuticals;Pharmacologic Substance;Pharmacological Substance;Phase;Physiologic;Physiological;Preparation;Production;Rat;Rats Mammals;Rattus;Reporting;Research;Residual;Residual State;Residual Volume;Risk;Sbir;Sbirs (R43/44);Sis Cytokines;Safety;Schools;Small Business Innovation Research;Small Business Innovation Research Grant;Solutions;Spinal Cord Lesions;Staging;Tacrolimus;Taxes;Techniques;Technology;Testing;Therapeutic Index;Toxic Effect;Toxicities;Translations;Treatment Efficacy;Treatment Side Effects;United States National Institutes Of Health;Universities;Urinary Retention;Urinary Tract Infection;Urinary Tract Infectious Disease;Urine;Urine Urinary System;Urothelium;Work;Afferent Nerve;Base;Botulinum Neurotoxin;Chemoattractant Cytokine;Chemokine;Comparative Efficacy;Compare Efficacy;Design;Designing;Detrusor Muscle;Developmental;Drug Detection;Drug Testing;Drug/Agent;Experience;Fluid;Health Care;High Risk;Improved;Intervention Efficacy;Interventional Strategy;Intravesical;Irritation;Liquid;Lower Urinary Tract Symptoms;Minimal Risk;Nano Particle;Nano Scale Science;Nano Tech;Nano Technology;Nanoparticle;Nanotech;Neurotransmitter Release;Painful Bladder Syndrome;Scale Up;Sensory Nerve;Side Effect;Therapeutic Efficacy;Therapeutically Effective;Therapy Adverse Effect;Therapy Efficacy;Treatment Adverse Effect;Urinary;Urinary Bladder