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Transcranial route of brain targeted delivery of methadone in oil.

Pathirana W, Abhayawardhana P, Kariyawasam H, Ratnasooriya WD - Indian J Pharm Sci (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Pharmacy, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo 8, Sri Lanka.

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 mug/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 mug/0.2 ml, 104 mug/0.2 ml and 208 mug/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.

No MeSH data available.


Antinociceptive effects with time using the hotplate and tail flick tests for groups 3 and 5.Left y-axis is for the curves A and B and right y-axis for curves C and D. Curve A represents hot plate test result of group 5 treated with transcranial methadone mid test dose (–■–) and Curve B represents group 3 control treated with transcranial blank oil (–◊–), Curve C represents tail flick test results of group 5 treated with transcranial methadone mid test dose (–▲–) and Curve D control of group 3 treated with transcranial blank oil (…○…).
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Figure 0003: Antinociceptive effects with time using the hotplate and tail flick tests for groups 3 and 5.Left y-axis is for the curves A and B and right y-axis for curves C and D. Curve A represents hot plate test result of group 5 treated with transcranial methadone mid test dose (–■–) and Curve B represents group 3 control treated with transcranial blank oil (–◊–), Curve C represents tail flick test results of group 5 treated with transcranial methadone mid test dose (–▲–) and Curve D control of group 3 treated with transcranial blank oil (…○…).

Mentions: Group 2 which was treated with oral administration of methadone hydrochloride 316.5 μg/ml shows a significant prolongation of the reaction time in the hot plate and tail flick tests from the first hour up to the sixth hour compared to the oral control group 1 treated with distilled water (fig. 1). When the group 4 animals were treated with 41.6 μg/0.2 ml low test dose of transcranial methadone solution, a significant analgesic effect was seen only in the first hour after treatment in the hot plate test, while the effect was significant in both the first and second hours in the tail flick test compared to control group 3 treated with 0.2 ml of transcranial blank oil (fig. 2). When compared to the blank oil control group 3, the 104 μg/0.2 ml mid test dose in group 5 exerted significant antinociceptive effects in the first and second hours after the transcranial treatment in the hot plate test as well as in the tail flick test (fig. 3). A similar significant antinociceptive effect was observed in group 6 following the 208 μg/0.2 ml high test dose transcranial methadone application in the first 3 h after treatment in the hot plate test and first 4 h after treatment in the tail flick test compared with the transcranial blank oil control group 3 (fig. 4). There was no significant difference between the oral negative control group 1 and the transcranial blank oil control group 3 in both hot plate and tail flick tests.


Transcranial route of brain targeted delivery of methadone in oil.

Pathirana W, Abhayawardhana P, Kariyawasam H, Ratnasooriya WD - Indian J Pharm Sci (2009)

Antinociceptive effects with time using the hotplate and tail flick tests for groups 3 and 5.Left y-axis is for the curves A and B and right y-axis for curves C and D. Curve A represents hot plate test result of group 5 treated with transcranial methadone mid test dose (–■–) and Curve B represents group 3 control treated with transcranial blank oil (–◊–), Curve C represents tail flick test results of group 5 treated with transcranial methadone mid test dose (–▲–) and Curve D control of group 3 treated with transcranial blank oil (…○…).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2865784&req=5

Figure 0003: Antinociceptive effects with time using the hotplate and tail flick tests for groups 3 and 5.Left y-axis is for the curves A and B and right y-axis for curves C and D. Curve A represents hot plate test result of group 5 treated with transcranial methadone mid test dose (–■–) and Curve B represents group 3 control treated with transcranial blank oil (–◊–), Curve C represents tail flick test results of group 5 treated with transcranial methadone mid test dose (–▲–) and Curve D control of group 3 treated with transcranial blank oil (…○…).
Mentions: Group 2 which was treated with oral administration of methadone hydrochloride 316.5 μg/ml shows a significant prolongation of the reaction time in the hot plate and tail flick tests from the first hour up to the sixth hour compared to the oral control group 1 treated with distilled water (fig. 1). When the group 4 animals were treated with 41.6 μg/0.2 ml low test dose of transcranial methadone solution, a significant analgesic effect was seen only in the first hour after treatment in the hot plate test, while the effect was significant in both the first and second hours in the tail flick test compared to control group 3 treated with 0.2 ml of transcranial blank oil (fig. 2). When compared to the blank oil control group 3, the 104 μg/0.2 ml mid test dose in group 5 exerted significant antinociceptive effects in the first and second hours after the transcranial treatment in the hot plate test as well as in the tail flick test (fig. 3). A similar significant antinociceptive effect was observed in group 6 following the 208 μg/0.2 ml high test dose transcranial methadone application in the first 3 h after treatment in the hot plate test and first 4 h after treatment in the tail flick test compared with the transcranial blank oil control group 3 (fig. 4). There was no significant difference between the oral negative control group 1 and the transcranial blank oil control group 3 in both hot plate and tail flick tests.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Pharmacy, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo 8, Sri Lanka.

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 mug/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 mug/0.2 ml, 104 mug/0.2 ml and 208 mug/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.

No MeSH data available.