Preparation, In Vitro and In Vivo Evaluation of Nanoemulsion In Situ Gel for Transnasal Delivery of Traditional Chinese Medicine Volatile Oil from <i>Ligusticum sinense</i> Oliv.cv. Chaxiong

Abstract

Ischemic stroke is a difficult-to-treat brain disease that may be attributed to a limited therapeutic time window and lack of effective clinical drugs. Nasal–brain administration is characterized by low systemic toxicity and is a direct and non-invasive brain targeting route. Preliminary studies have shown that the volatile oil of Chaxiong (VOC) has an obvious anti-ischemic stroke effect. In this work, we designed a nanoemulsion thermosensitive in situ gel (VOC-NE-ISG) loaded with volatile oil of Chaxiong for ischemia via intranasal delivery to rat brain treatment of cerebral ischemic stroke. The developed VOC-NE-ISG formulation has a suitable particle size of 21.02 ± 0.25 nm and a zeta potential of −20.4 ± 1.47 mV, with good gelling ability and prolonged release of the five components of VOC. The results of in vivo pharmacokinetic studies and brain targeting studies showed that intranasal administration of VOC-NE-ISG could significantly improve the bioavailability and had excellent brain-targeting efficacy of nasal-to-brain delivery. In addition, the results of pharmacodynamics experiments showed that both VOC-NE and VOC-NE-ISG could reduce the neurological deficit score of model rats, reducing the size of cerebral infarction, with a significant effect on improving ischemic stroke. Overall, VOC-NE-ISG may be a promising intranasal nanomedicine for the effective treatment of ischemic stroke.

Keywords

• volatile of <i>Ligusticum sinense</i> Oliv.cv. Chaxiong
• nanoemulsion
• in situ gel
• nasal administration