Bladder drug delivery using intravesical liposomes to treat overactive bladder

描述（由申请人提供）：Lipella Pharmaceuticals Inc.由美国国立卫生研究院小企业创新与研究（SBIR）赠款，开发膀胱内脂质体纳米颗粒治疗膀胱过度活动症（OAB），间质性膀胱炎/膀胱疼痛综合征（IC/PBS）。目前的SBIR将允许Lipella扩大其专利申请组合，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顽固性下尿路症状的治疗。然而，BoNT治疗伴随着许多不良反应，如逼尿肌收缩力受损、大的排尿后残留量和尿潴留。我们推测，通过将其作用仅限于尿道和尿道下裂空间，可以大大减少BoNT的不良反应。我们可以通过使用脂质体纳米技术实现BoNT局部递送到膀胱尿道的目的。 该项目的第一阶段资金支持实验室规模的开发，以实现基于脂质体的BoNT液体滴注，在膀胱中具有显著的生理作用，对膀胱组织学无任何不良影响。II期所述的研究将检验脂质体包封比目前使用的膀胱镜下注射BoNT的方法提供更高的治疗功效和安全性（改善治疗指数）的假设。此外，与小分子量强效药物（他克莫司）相比，我们将优化BoNT的脂质体平台技术，以实现脂质体制剂的预期产品稳定性和可维持商业用途的有效期。 这项SBIR-II的资助将使Lipella能够将我们的技术与其他膀胱内药物递送应用联系起来，并将使Lipella Pharmaceutical能够准备IND包装以供监管提交。自最初的发现和从学术到生物技术创业的转变以来，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的减少，SBIR-II对Lipella未来的重要性不容低估，它实现了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。 公共卫生相关性：Lipella Pharmaceuticals Inc.由美国国立卫生研究院小企业创新与研究（SBIR）赠款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递送技术。开发一种安全有效的脂质体液体药物输送到膀胱中，而不需要内窥镜干预和全身毒性，尿刺激或保留的风险最小是一个优先事项。药物递送阻断膀胱炎症将是该项目的目标，该资助的成功完成将使Lipella Pharmaceuticals能够准备基于脂质体的药物递送IND的监管提交。

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.