Nanoparticle Formulation of a Drug for Direct Inner Ear Therapy

耳鸣的治疗方法有哪些？耳鸣的治疗方法有哪些？NeuroSystec与Kresge听力研究所（KHRI）和汉诺威医科大学（MHH）的基础和临床科学家合作，已：1）证实加环利定（NST-001）在耳鸣动物模型中有效，2）通过同情治疗抑制人类耳鸣。然而，为了有效和实用的耳鸣控制，NST-001必须被配制用于慢性和长期施用。在这方面，NST-001不够稳定;溶解度不够;并且在给药期间存在导管和输送系统其他组件损失的问题。在一项突破性的发现中，NeuroSystec开发了一种固体药物输送装置，解决了NST-001持续和长期给药的问题。然而，尽管该技术将允许对许多患者进行治疗，但在已经装配有耳蜗植入物（CI）的那些患者中，它仍然会遭受与药物损失相关的问题。当通过CI或CI附近给药溶液时，用于制造CI的材料将从溶液中吸附大量NST-001。为了解决这个药物递送问题，NeuroSystec计划采用药物的纳米颗粒制剂：1）将药物保持在能够通过专有抗菌过滤器的稳定悬浮液中; 2）避免药物在释放到耳蜗期间或之后损失到CI组分中。为了实现这一目标，NeuroSystec计划在拟议项目期间实现以下目标：具体目标1。改进现有的混合技术，以用于由GMP材料制成的纳米颗粒的溶剂置换法，这些材料被批准用于人体植入[例如，聚（丙交酯-共-乙交酯）、PLGA或等效材料]，并将纳米颗粒与轻油（甘油三酯）共配制以调节其密度、沉降时间和药物结合性质。具体目标2。开发用于在制造后用NST-001装载纳米颗粒的方法，这将允许在患有CI的患者中使用该制剂。具体目标3。开发与纳米颗粒制造（传统方法）同时使用NST-001装载纳米颗粒的方法。

DESCRIPTION (provided by applicant): There is currently no reliable therapy and no cure for tinnitus. NeuroSystec, in collaboration with basic and clinical scientists at the Kresge Hearing Research Institute (KHRI) and the Medical University of Hannover (MHH), has: 1) confirmed that gacyclidine (NST-001) is effective in animal models for tinnitus and 2) suppresses human tinnitus through compassionate therapy. However, for effective and practical tinnitus control, NST-001 must be formulated for chronic and long-term administration. In this regard, NST-001 is not sufficiently stable; not sufficiently soluble; and suffers from problems of loss to catheters and other components of delivery systems during administration. In a breakthrough discovery, NeuroSystec has developed a solid drug-delivery device which solves the problems of sustained and long-term administration of NST-001. However, while this technology will allow therapy for many patients, it will still suffer from problems associated with drug loss in those patients who have been fitted with a cochlear implant (CI). The materials used to fabricate CIs will adsorb a substantial fraction of NST-001 from solutions, when these solutions are administered through or near the CI. To solve this drug delivery problem, NeuroSystec plans to employ a nanoparticle formulation of the drug to: 1) keep the drug in a stable suspension capable of passing through a proprietary antibacterial filter; and 2) avoid loss of drug to CI components during or after release into the cochlea. To achieve this end, NeuroSystec plans to meet the following goals during the period of the proposed project: Specific aim 1. Improve existing mixing technology to be used in the solvent-displacement method for nanoparticles fabricated from GMP materials that are approved for human implantation [e.g., poly(lactide-co-glycolide), PLGA or equivalent material] and to co-formulate nanoparticles with light oils (triglycerides) to adjust their densities, sedimentation times and drug-binding properties. Specific aim 2. Develop methodologies for loading nanoparticles with NST-001 after fabrication that would allow for use of the formulation in patients fitted with a CI. Specific aim 3. Develop methodologies for loading nanoparticles with NST-001 concurrently with nanoparticle fabrication (the conventional method).