Development and Translation of NanoBEO, a Nanotechnology-Based Delivery System of Bergamot Essential Oil Deprived of Furocumarins, in the Control of Agitation in Severe Dementia.

Damiana Scuteri,Roberta Cassano,Annarita S Laganà,Pierluigi Nicotera,Takaaki Komatsu,Soh Katsuyama,Hirokazu Mizoguchi,Sonia Trombino,Paolo Tonin,Annagrazia Adornetto,Chizuko Watanabe,Shinobu Sakurada,Kengo Hamamura,Maria Tiziana Corasaniti,Luigi Antonio Morrone,Laura Rombolà,Tsukasa Sakurada,Giacinto Bagetta,Rossella Russo

doi:10.3390/pharmaceutics13030379

Abstract

Dementia is one of the most common causes of disability worldwide characterized by memory loss, cognitive impairment, and behavioral and psychological symptoms (BPSD), including agitation. Treatment of the latter consists of the off-label use of harmful atypical antipsychotics, though a significant reduction is afforded by pain control. The use of an essential oil endowed with analgesic properties and devoid of toxicity would represent an important option for the management of agitation in dementia. Therefore, the aim of this study was to engineer a nanotechnology delivery system based on solid lipid nanoparticles loaded with bergamot essential oil (BEO) and devised in the pharmaceutical form of an odorless cream (NanoBEO) to confirm its analgesic efficacy for further development and application to control agitation in dementia. BEO has proven strong antinociceptive and anti-allodynic properties and, in its bergapten-free form, it is completely devoid of phototoxicity. NanoBEO has been studied in vivo confirming the previously reported analgesic activity of BEO to which is now added its anti-itching properties. Due to the nanotechnology delivery system, the stability of titrated BEO components is guaranteed. Finally, the latter invention, currently under patent consideration, is smell-devoid allowing efficacy and safety to be established in double-blind clinical trials; until now the latter studies have been impeded in aromatherapy by the strong odor of essential oils. A clinical trial NCT04321889 has been designed to provide information about the efficacy and safety of NanoBEO on agitation and pain in patients suffering from severe dementia.

Highlights

The improvement of life expectancy over the 21st century has led to demographic aging with a steady increase of age-related neurodegenerative pathologies [1]
The results indicated the presence of 27% of linalool, 31% of linalyl acetate, and 36% of limonene
After two and six months of light exposure, these percentages declined by 10% and 18%, respectively, with no further degradation at twelve months, demonstrating that α-TFS-SLNs effectively slowed down the degradation of bergamot essential oil (BEO)-BF

Summary

Introduction

The improvement of life expectancy over the 21st century has led to demographic aging with a steady increase of age-related neurodegenerative pathologies [1]. The inadequate pain treatment received by cognitively impaired patients is often due to their reduced or absent communication skills that prevent self-reporting: unrelieved pain is involved in the development of agitation [10], one of the most challenging behavioral and psychological symptoms of dementia (BPSD), known as neuropsychiatric symptoms (NPS). This leads to the off-label use of antidepressants and atypical antipsychotics that double the risk of death for cardiocerebrovascular accidents in these patients [11]. In the frame of the current novel severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) pandemic, it is the elderly who paid the highest price [12], and COVID-19

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