Bladder drug delivery using intravesical liposomes to treat overactive bladder

描述(由申请人提供)：Lipella制药公司已得到美国国立卫生研究院小型企业创新和研究(SBIR)赠款的资助，用于开发膀胱内脂质体纳米颗粒，用于治疗膀胱过度活跃(OAB)、间质性膀胱炎/疼痛膀胱综合征(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输送技术。近年来，肉毒杆菌神经毒素(BoNT)膀胱内注射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下尿路顽固性症状的治疗方法。然而，BONT治疗伴随着许多不良反应，如逼尿肌收缩能力受损，排尿后残留量大和尿潴留。我们假设，通过将其作用仅限于尿路上皮和尿路下层间隙，BONT的不良影响可以显著减少。利用脂质体纳米技术可以达到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，以脂质体为基础的液体滴注BONT，在膀胱中具有显著的生理作用，而不会对膀胱组织学产生任何不利影响。第二阶段描述的研究将检验这样一种假设，即脂质体包裹比目前使用的膀胱镜注射BONT方法提供更高的治疗效果和安全性(改善治疗指数)。此外，与小分子强效药物(他克莫司)相比，我们将优化BONT的脂质体平台技术，以实现所需的脂质体配方的产品稳定性和可持续商业使用的货架期。这项SBIR-II的资金将使Lipella能够将我们的技术与更多的膀胱内药物输送应用连接起来，并将使Lipella制药公司能够准备IND包以供监管机构提交。自最初发现利佩拉，并从学术初创公司转变为生物技术初创公司以来，利佩拉已经走过了很长一段路。随着严峻的经济形势和早期生物技术风险投资的减少，SBIR-II对Lipella未来的重要性不可低估，它完成了NIH将研究发现从实验室带入临床的重要使命。在NIH的支持下，Lipella可以成为一家可持续发展的纳税公司，改善美国人的医疗保健，支持当地和国家经济。 与公共健康相关：Lipella制药公司已得到美国国立卫生研究院小型企业创新和研究(SBIR)赠款的资助，用于开发膀胱内脂质体，目前正在扩大其产品组合，以开发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给药进入膀胱，不需要内窥镜干预，并将全身毒性、尿路刺激或滞留的风险降至最低是当务之急。阻止膀胱炎的药物输送将是这一项目的目标，这笔赠款的成功完成将使Lipella制药公司能够准备一份基于脂质体的药物输送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.