A review of literature on Compound 21-loaded gelatin nanoparticle: a promising nose-to-brain therapy for multi-infarct dementia

Abstract

AbstractMulti-infarct dementia (MID) is described as a chronic progressive decline in cortical cognitive function due to the occurrence of multiple infarcts in the cerebral vascularization throughout the gray and white matter. Current therapies of MID mostly focus only on slowing down MID progression and symptomatic medications. A novel therapy which is able to provide both preventive and curative properties for MID is of high interest. The purpose of this review is to identify the potential of Compound 21 (C21) gelatin nanoparticle through the nose-to-brain route as therapy for MID. C21, an angiotensin II type 2 receptor (AT2R) agonist, has shown to reduce the size of cerebral infarct in rodent models, resulting in the preservation and improvement of overall cognitive function and prevention of secondary neurodegenerative effects. It is also shown that C21 decreases neuronal apoptosis, improves damaged axons, and encourage synapse development. The challenge remains in preventing systemic AT2R activation and increasing its low oral bioavailability which can be overcome through nose-to-brain administration of C21. Nose-to-brain drug delivery of C21 significantly increases drug efficiency and limits C21 exposure in order to specifically target the multiple infarcts located in the cerebral cortex. Adhering C21 onto gelatin nanoparticles may enable longer contact time with the olfactory and the trigeminal nerve endings, increasing the potency of C21. In summary, treatment of C21 gelatin nanoparticle through nose-to-brain delivery shows high potential as therapy for vascular dementia. However, clinical trials must be further studied in order to test the safety and efficacy of C21.