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. 已获得美国国立卫生研究院小企业创新与研究中心 (SBIR) 的资助，用于开发膀胱内脂质体纳米颗粒，用于治疗膀胱过度活动症 (OAB)、间质性膀胱炎/膀胱疼痛综合征 (IC/美国公共广播公司）。目前的 SBIR 将使 Lipella 能够扩大其有关使用脂质体作为平台技术的特定膀胱内脂质体递送技术的专利申请组合。近年来，膀胱内注射肉毒神经毒素 (BoNT) 彻底改变了与特发性 OAB 或神经源性逼尿肌过度活动相关的顽固性下尿路症状的治疗。然而，BoNT 治疗伴随着许多副作用，例如逼尿肌收缩力受损、排尿后残余量大和尿潴留。我们假设，通过将 BoNT 的作用仅限于尿路上皮和尿路上皮下间隙，可以大大减少 BoNT 的副作用。我们可以利用脂质体纳米技术实现将BoNT局部递送至膀胱尿路上皮的目的。该项目的第一阶段资金支持实验室规模的开发，以脂质体为基础的 BoNT 液体滴注，对膀胱具有显着的生理作用，且对膀胱组织学没有任何不利影响。 II 期描述的研究将验证脂质体封装比目前使用的膀胱镜注射 BoNT 方法提供更高的治疗功效和安全性（提高治疗指数）的假设。此外，我们将优化BoNT的脂质体平台技术，与小分子量强效药物（他克莫司）相比，以实现所需的脂质体配方产品稳定性和可维持商业使用的保质期。该 SBIR-II 的资助将使 Lipella 能够将我们的技术与其他膀胱内药物输送应用联系起来，并使 Lipella Pharmaceutical 能够准备 IND 包以供监管提交。自从最初的发现和从学术到生物技术初创公司的转化以来，利佩拉已经取得了长足的进步。随着经济形势的严峻和早期生物技术风险投资资金的减少，SBIR-II 对 Lipella 未来的重要性不容低估，它履行了 NIH 将研究发现从实验室推向临床的重要使命。在 NIH 的支持下，Lipella 可以成为一家可持续的纳税公司，改善美国人的医疗保健并支持地方和国家经济。公共健康相关性：Lipella Pharmaceuticals Inc. 已获得美国国立卫生研究院小企业创新与研究中心 (SBIR) 的资助，用于开发膀胱内脂质体，目前正在将其产品组合扩展到膀胱内脂质体药物输送技术。开发一种安全有效的脂质体液体将药物输送到膀胱中，无需内窥镜干预，并且将全身毒性、尿路刺激或潴留的风险降到最低是当务之急。阻断膀胱炎症的药物输送将是该项目的一个目标，这笔拨款的成功完成将使 Lipella Pharmaceuticals 能够准备基于脂质体的药物输送 IND 的监管提交。