Bladder drug delivery using intravesical liposomes to treat overactive bladder

使用膀胱内脂质体进行膀胱药物输送治疗膀胱过度活动症

基本信息

批准号：
8119224
负责人：
JONATHAN H KAUFMAN
金额：
$ 49.73万
依托单位：
LIPELLA PHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-06 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8119224
关键词：
Adverse effects Affect American Biochemistry Biophysics Biotechnology Bladder Bladder Urothelium Bontoxilysin Businesses Capital Financing Catheterization Clinic Collaborations Cystoscopes Data Development Doctor of Philosophy Drug Delivery Systems Drug Formulations Funding Future Grant Healthcare Histology Inflammation Injection of therapeutic agent Interstitial Cystitis Intervention Intravesical Injections Laboratories Legal patent Licensing Life Liposomes Liquid substance Marketing Methods Mission Molecular Molecular Weight Nanotechnology Nerve Endings Overactive Bladder Patients Pennsylvania Pharmaceutical Preparations Pharmacologic Substance Phase Physiological Preparation Production Rattus Reporting Research Residual state Residual volume Risk Safety Schools Small Business Innovation Research Grant Solutions Spinal Cord Lesions Staging Tacrolimus Taxes Techniques Technology Testing Therapeutic Index Toxic effect Translations Treatment Efficacy United States National Institutes of Health Universities Urinary Retention Urinary tract infection Urine Urothelium Work afferent nerve base chemokine comparative efficacy design detrusor muscle drug testing experience high risk improved intravesical irritation lower urinary tract symptoms minimal risk nanoparticle neurotransmitter release painful bladder syndrome scale up urinary

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：Lipella Pharmaceuticals Inc.已由美国国立卫生研究院小型企业创新与研究（SBIR）资助，以开发静脉内脂质体纳米粒子来治疗过度活跃的膀胱（OAB），间质囊炎/性囊炎/性腹腔囊肿综合症（IC/PBS）。当前的SBIR将允许Lipella使用脂质体作为平台技术扩展其专利申请的投资组合。近年来，肉毒神经毒素（BONT）的静脉注射彻底改变了治疗与特发性OAB或神经源性逼尿肌过度活跃相关的可怕的较低尿路症状。然而，许多不良反应（例如迫害者的收缩力，大量的后残余体积和尿retention留）参加了BONT治疗。我们假设可以通过将其作用仅限于尿皮上皮和腹皮空间，从而大大降低BONT的不利影响。我们可以通过使用脂质体纳米技术来实现将BONT局部传递到膀胱尿皮上的目标。该项目的第一阶段资金支持实验室规模的发展，用于基于脂质体的液体液体滴注BONT，对膀胱的生理作用显着，对膀胱组织学没有任何不利影响。 II期描述的研究将检验以下假设：脂质体封装比当前使用的BONT的膀胱注射方法更高的治疗功效和安全性（改善治疗指数）。此外，与小型分子量有效药物（他克莫司）相比，我们还将优化脂质体平台技术，以实现可以维持商业用途的脂质体配方和保质期的所需产品稳定性。该SBIR-II的资金将使Lipella能够将我们的技术桥接到其他静脉内药物输送应用中，并允许Lipella Pharmaceutical来准备IND包装以进行监管提交。自从最初发现和翻译从学术到生物技术创业公司的翻译以来，Lipella已经走了很长一段路。随着早期生物技术风险投资资金的挑战性经济状况和减少，这种SBIR-II对Lipella的未来的重要性不能低估，并且可以实现NIH将研究发现从LAB带到诊所的重要任务。在NIH的支持下，Lipella可以成为一家可持续的纳税公司，以改善美国人的医疗保健并支持当地和国民经济。公共卫生相关性：Lipella Pharmaceuticals Inc.由美国国立卫生研究院小型企业创新与研究（SBIR）资助以开发静脉内脂质体，现在正在将其投资组合扩展到静脉内脂质体药物输送技术。不需要内窥镜干预，尿液毒性，尿液刺激或保留率最小的情况，将药物的安全有效脂质体液体递送到膀胱中的开发是优先的。输送到阻断膀胱炎症的药物将是该项目的目标，并且该赠款的成功完成将使Lipella Pharmaceuticals能够准备基于脂质体的药物输送IND的监管提交。