Bladder drug delivery using intravesical liposomes to treat overactive bladder

描述（由申请人提供）：Lipella制药公司获得了美国国立卫生研究院小企业创新与研究（SBIR）的资助，用于开发膀胱内脂质体纳米颗粒，以治疗膀胱过动症（OAB）、间质性膀胱炎/膀胱疼痛综合征（IC/PBS）。目前的SBIR将允许Lipella扩展其专利申请组合，涉及使用脂质体作为平台技术的特定膀胱内脂质体递送技术。近年来，膀胱内注射肉毒杆菌神经毒素（BoNT）已经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难治性下尿路症状的治疗。然而，BoNT治疗有许多不良反应，如逼尿肌收缩功能受损、尿后残留体积大和尿潴留。我们假设BoNT的副作用可以通过限制其仅作用于尿路上皮和上皮下空间而大大减少。我们可以通过脂质体纳米技术实现局部给药到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发展，以脂质体为基础的BoNT液体灌注，在膀胱中具有显着的生理作用，而不会对膀胱组织学产生任何不良影响。II期研究将验证脂质体包封比目前使用的膀胱镜注射BoNT方法具有更高的治疗效果和安全性（提高治疗指数）。此外，我们将优化BoNT脂质体平台技术，与小分子量强效药物（他克莫司）进行比较，以达到所需的脂质体制剂稳定性和可维持商业使用的保质期。此次SBIR-II的资金将使Lipella能够将我们的技术应用于更多的膀胱内给药应用，并将使Lipella制药公司准备IND包提交监管机构。从最初的发现和从学术到生物技术创业的转化，Lipella已经走过了漫长的道路。随着具有挑战性的经济条件和早期生物技术风险投资资金的减少，该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带到临床的重要使命。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，支持地方和国家经济。

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.