Intranasal CDNF and MANF Polypeptide Delivery via Absorption Enhancers
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Solution Overview
Problem
Current methods for treating central nervous system diseases, such as Alzheimer's and Parkinson's, face challenges in delivering therapeutic agents across the blood-brain barrier, particularly for high molecular weight proteins like CDNF and MANF, which have shown efficacy in animal models but require effective nasal penetration.
Innovation Solution
CDNF and MANF polypeptides are formulated for intranasal administration, leveraging their chemical and biological characteristics to bypass the blood-brain barrier, allowing direct transport to the central nervous system, where they can treat various central nervous system diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high molecular weight proteins like CDNF and MANF are administered intranasally, then they can bypass the blood-brain barrier and reach the central nervous system, but their nasal penetration ability is unpredictable and decreased permeability across nasal mucosa occurs
Solution Approach 1:
The patent employs absorption enhancers as intermediary substances that facilitate the transport of high molecular weight proteins across the nasal mucosa. These enhancers temporarily modify the mucosal barrier properties or create transport pathways, enabling CDNF and MANF to penetrate the nasal epithelium and reach the olfactory bulb and central nervous system with improved reliability and predictability.
2Ease of operation
If conventional routes of drug administration are used, then oral administration is simple, but the blood-brain barrier and blood-cerebrospinal fluid barrier hinder the entrance of drugs into the central nervous system
Solution Approach 1:
The patent segments the drug delivery pathway by bypassing the systemic circulation and blood-brain barrier entirely. Instead of administering drugs systemically and hoping they cross the barrier, the invention delivers drugs directly to the nasal cavity, where they can access the central nervous system through the olfactory route, effectively dividing the delivery system into two independent pathways: nasal administration and direct brain access.
3Reliability
If invasive neurosurgical methods are used for convection-enhanced delivery, then direct brain region targeting is achieved, but surgical intervention and catheter placement are required
Solution Approach 1:
The patent inverts the conventional approach by delivering the drug to the brain through the nose rather than inserting devices into the brain. Instead of pushing the drug from the brain outward through catheters, the invention allows the drug to naturally travel from the nasal cavity into the central nervous system through the olfactory bulb, eliminating the need for surgical intervention while maintaining reliable delivery.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Intranasal administration of CDNF and MANF polypeptides demonstrates significant brain penetration and therapeutic efficacy in animal models, including reduced infarct volume and improved functional recovery in stroke and neuroprotective effects, highlighting their potential for treating central nervous system diseases.
Implementation Method 1
CDNF and MANF polypeptides are therefore able to bypass blood-brain-barrier through nasal route and reach the CNS
Data Source
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AI summary
The present invention is directed to a composition for intranasal administration comprising a CDNF polypeptide for use in the intranasal treatment of a central nervous system disease, such as Alzheimer's disease, Parkinson's disease, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, dementia with Lewy bodies, mild cognitive impairment, Huntington's disease, traumatic brain injury and stroke. The present invention is also directed to a composition for intranasal administration comprising a MANF polypeptide for use in the intranasal treatment of a central nervous system disease.