JOURNAL ARTICLE
REVIEW
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[Development of Noninvasive Drug Delivery Systems to the Brain for the Treatment of Brain/Central Nervous System Diseases].

 In general, the blood-brain barrier (BBB) poses a major challenge to drug development efforts targeting brain/central nervous system (CNS) diseases, since it limits the distribution of systemically administered therapeutics to the brain/ CNS. Therefore, the development of effective strategies for enhancing drug delivery to the brain has been a topic of great interest in both the clinical and pharmaceutical fields. Intranasal administration has been noted as a method for noninvasive delivery of a drug to the brain/CNS by bypassing the BBB via the "nose-to-brain" route. This nose-to-brain delivery system has the potential to be highly versatile, and a combination of this system with new drugs and siRNA shows promise in the treatment of CNS diseases. Cell-penetrating Tat peptide-modified block copolymer micelles have the potential for improving mucosal permeability and nose-to-brain transport efficiency. In addition, nano-sized drug carriers can improve nose-to-brain delivery through their ability to increase the stability of encapsulated drugs against biological degradation in the nasal cavity and brain/CNS. In this review, we introduce the assessment of and mechanisms for delivery to the brain after intranasal drug/siRNA administration with our cell-penetrating peptide-modified nano-sized polymer micelles. Our findings show that the use of polymer micelles with surface modification by cell-penetrating peptides for intranasal administration enables the noninvasive delivery of therapeutic agents to the brain/CNS by increasing the nose-to-brain transfer of the drug or siRNA administered from the nasal cavity.

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