Biodegradable Implant for Sustained Trans-Nasal Delivery to the Brain

A sustained-release delivery vehicle for the treatment of brain diseases

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Source: mrithi Padmakumar, Gregory Jones, Grishma Pawar, Olga Khorkova, Jane Hsiao, Jonghan Kim, Mansoor M. Amiji, Benjamin S. Bleier, Minimally Invasive Nasal Depot (MIND) technique for direct BDNF AntagoNAT delivery to the brain, Journal of Controlled Release, Volume 331, 2021, Pages 176-186, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2021.01.027.

 

 

INV-20104

 

Central Nervous System (CNS) diseases refer to those groups of neurological disorders particularly affecting the central nervous system comprised of the brain and spinal cord. They arise due to multiple factors such as neurodegeneration, infections leading to potential damage, trauma, metabolic disorders, tumor, stroke etc. The common symptoms of CNS disorders are associated with the loss of intact coordination between the nervous system circuits which results in disruptions of the motor (such as tremors, ataxias) and nonmotor activities (such as dementia, cognitive decline, behavior disturbances). The progressive loss or depletion of neurons producing certain neurotransmitters and belonging to particular brain regions leads to diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). AD and PD affect nearly 5 million and 1 million of the current American population respectively, and their incidences ascend with the aging population. These diseases have been considered incurable and the existing therapeutic strategies are designed to relieve the symptoms. Many reports indicate that these common neurological diseases pose a staggering financial burden annually to the American healthcare system, totaling up to $800 billion per year. These situations underline the critical need for developing more approaches to prevent and effectively treat these brain disorders.

The existence of the blood-brain barrier (BBB) hindering the penetration of therapeutics and restricting the overall drug uptake is the major limiting factor for the development, successful translation, and clinical adoption of many treatment strategies for CNS diseases.

 

This invention focuses on the development of a biodegradable polymeric implant (typically around 10 mm by 3 mm cylindrical device) that can be placed in the nasal cavity through minimally invasive nasal depot (MIND) surgical approach. This implant will delivery therapeutic molecules, including biologically-active compounds such as antibodies, peptides, and nucleic acid therapeutics, into the brain continuously through this depot. The implant can be tailored for a specific duration of release and biodegradation based on the dimensions and molecular weight/type of biodegradable polymer used. This versatility in design is critical for the development of delivery systems for a broad spectrum of payloads in the treatment of CNS diseases.

 

- Considering the unmet emergency to explore safer, less invasive, and patient-compliant modes of delivering therapeutics to CNS across BBB, the proposed trans-nasal approaches hold enormous potential

- Implants can be developed from a wide variety of biodegradable polymers/ copolymers and can entrap a wide variety of therapeutics such as drugs, small molecules, nucleic acids, peptides, proteins, etc.,

- Microfabrication technique ensures uniformity and homogeneity of size, dimensions, morphology, and surface features of implants which critically determines its degradation rate and also controls the release rate of entrapped therapeutics

 

- Development of sustained-release delivery vehicle for the treatment of brain diseases

 

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