Transcranial route of brain targeted delivery of methadone in oil

Abstract

The unique anatomical arrangement of blood vessels and sinuses in the human skull and the brain, the prevalence of a high density of skin appendages in the scalp, extracranial vessels of the scalp communicating with the brain via emissary veins and most importantly, the way that the scalp is used in Ayurvedic medical system in treating diseases associated with the brain show that a drug could be transcranially delivered and targeted to the brain through the scalp. The present study was to investigate by measuring the antinociceptive effect on rats whether the opioid analgesic methadone could be delivered and targeted to the brain by transcranial delivery route. A non aqueous solution of methadone base in sesame oil was used for the application on the scalp. Animal studies were carried out using six groups of male rats consisting of group 1, the oral control treated with distilled water 1 ml; group 2, the oral positive control treated with methadone hydrochloride solution 316.5 μg/ml; group 3, the negative control treated transcranially with the blank sesame oil 0.2 ml and three test groups 4, 5 and 6 treated with three different dose levels of the transcranial oil formulation of methadone base, 41.6 μg/0.2 ml, 104 μg/0.2 ml and 208 μg/0.2 ml, respectively. The antinociceptive effects were examined by subjecting the rats to the hot plate and tail flick tests. The two higher concentrations of the three transcranial methadone formulations yielded response vs time curves showing nearly equal maximum antinociceptive effects similar to that of the oral positive control. Maximum analgesic effect after transcranial administration was observed between 1st and 2nd h and declined up to 6th hour. The results indicate that the transcranial brain targeted delivery of methadone base in the form of an oil based non aqueous solution results in statistically significant antinociceptive effects under experimental conditions. Therefore, it is possible to deliver central nervous system drugs through the proposed transcranial route when suitably formulated.

<i>Manasamitra vataka</i> and <i>Shirodhara</i> Treatments Preserve Slow Wave Sleep and Promote Sleep Continuity in Patients with Generalized Anxiety Disorder and Co-Morbid Generalized Social Phobia

“…However, the effect of external use of Brahmi oil (B. monnieri) has not been reported. Shirodhara treatment has been shown to produce anxiolytic effects as assessed by state-trait anxiety inventory [26][27][28][29] and Shirodhara effect could be through brain-targeted transcranial drug delivery 30,31 . The present study shows that Shirodhara with Brahmi oil considerably reduces the micro-arousals and helps in sleep continuity.…”

Comparative Clinical Evaluation of an Ayurvedic Regimen in the Management of Senile Dementia

“…This is also supported by Ashtanga Hridaya, i.e., Shirobasti is the most effective of all type of Moordha taila 13 . Study suggests that drug if suitably formulated can be delivered directly to the brain via transcranial route 30 . As the nervous system is mainly composed of lipoid tissue, the Ghrita being lipid in nature is quickly absorbed due to the rich vasculature of the scalp and gets distributed to different parts of the brain through the communicating veins (extracranial to intra cranial), exerting its influence on various centres, including the limbic system and the hypothalamus.…”

Ayurvedic medicinal plants for Alzheimer's disease: a review

“…Procedures like Shirodhara (gentle dripping of the medicated oil on the forehead), Shirobasti (a special leather cap is placed over the shaved head of a patient and medicated oil is poured and retained over the head for 30 to 45 minutes), ShiroAbhyanga (medicated oil is smeared on the head followed by a gentle massage), and ShiroSeka (medicated oil is poured over the head in a continuous stream) may also influence hormonal and cerebral blood flow levels to a degree similar to that of Ayurvedic massage as mentioned above [107-110]. While scientific studies regarding the permeation of the herbal components into the CNS through transcranial oleation therapies are lacking, recent work again points to the possibility that the endothelial cells facilitate the entry of the solutes through the frontal lobe and prefrontal cortex [109,110].…”