Low-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment

Mai Ahmed Tawfik, Mina Ibrahim Tadros, Magdy Ibrahim Mohamed, Sara Nageeb El-Helaly Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, EgyptCorrespondence: Mina Ibrahim TadrosCairo University, Kasr El-Aini Street, Cairo 11562, EgyptTel +20 1223620458Fa...

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Autores principales:	Tawfik MA, Tadros MI, Mohamed MI, Nageeb El-Helaly S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	agomelatine invasomes transdermal sonophoresis low frequency ultrasound. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3dc5f1f12f694287a2e7cf7bf14c89a3
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spelling	oai:doaj.org-article:3dc5f1f12f694287a2e7cf7bf14c89a32021-12-02T12:02:25ZLow-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment1178-2013https://doaj.org/article/3dc5f1f12f694287a2e7cf7bf14c89a32020-11-01T00:00:00Zhttps://www.dovepress.com/low-frequency-versus-high-frequency-ultrasound-mediated-transdermal-de-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mai Ahmed Tawfik, Mina Ibrahim Tadros, Magdy Ibrahim Mohamed, Sara Nageeb El-Helaly Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, EgyptCorrespondence: Mina Ibrahim TadrosCairo University, Kasr El-Aini Street, Cairo 11562, EgyptTel +20 1223620458Fax +20 223628426Email mina.tadros@pharma.cu.edu.egAim: Agomelatine (AGM) is the first melatonergic antidepressant. It suffers from low oral bioavailability (< 5%) due to extensive hepatic metabolism. The current work aimed to develop an alternative AGM-loaded invasomes to enhance transdermal drug bioavailability.Methodology: AGM-loaded invasomes were developed using two drug: lipid ratios (1:10 or 1:7.5), four terpene types (limonene, cineole, fenchone or citral) and two terpene concentrations (0.75% or 1.5%, w/v). They were characterized for drug entrapment efficiency (EE%), particle size (PS), zeta potential (ZP) and drug released percentages after 0.5h (Q0.5h) and 8h (Q8h). The optimum invasomes (I1, I2 and I4) were evaluated for morphology, drug-crystallinity, and ex-vivo drug flux. The variables influencing sonophoresis of the best achieved invasomal gel system (I2) were optimized including, ultrasound frequency (low, LFU or high, HFU), mode (pulsed or continuous), application period (10 min or 15 min) and duty cycle (50% or 100%). AGM pharmacokinetics were evaluated in rabbits following transdermal application of I2-LFU-C4 system, relative to AGM oral dispersion.Results: The superiority of I2 invasomes [comprising AGM and phosphatidylcholine (1:10) and limonene (1.5% w/v)] was statistically revealed with respect to EE% (78.6%), PS (313 nm), ZP (− 64 mV), Q0.5h (30.1%), Q8h (92%), flux (10.79 μg/cm2/h) and enhancement ratio (4.83). The optimum sonophoresis conditions involved application of LFU in the continuous mode for 15 min at a 100% duty cycle (I2-LFU-C4 system). The latter system showed significantly higher Cmax, and relative bioavailability (≈ 7.25 folds) and a similar Tmax (0.5 h).Conclusion: I2-LFU-C4 is a promising transdermal system for AGM.Keywords: agomelatine, invasomes, transdermal, sonophoresis, low frequency ultrasoundTawfik MATadros MIMohamed MINageeb El-Helaly SDove Medical Pressarticleagomelatineinvasomestransdermalsonophoresislow frequency ultrasound.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 8893-8910 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	agomelatine invasomes transdermal sonophoresis low frequency ultrasound. Medicine (General) R5-920
spellingShingle	agomelatine invasomes transdermal sonophoresis low frequency ultrasound. Medicine (General) R5-920 Tawfik MA Tadros MI Mohamed MI Nageeb El-Helaly S Low-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment
description	Mai Ahmed Tawfik, Mina Ibrahim Tadros, Magdy Ibrahim Mohamed, Sara Nageeb El-Helaly Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, EgyptCorrespondence: Mina Ibrahim TadrosCairo University, Kasr El-Aini Street, Cairo 11562, EgyptTel +20 1223620458Fax +20 223628426Email mina.tadros@pharma.cu.edu.egAim: Agomelatine (AGM) is the first melatonergic antidepressant. It suffers from low oral bioavailability (< 5%) due to extensive hepatic metabolism. The current work aimed to develop an alternative AGM-loaded invasomes to enhance transdermal drug bioavailability.Methodology: AGM-loaded invasomes were developed using two drug: lipid ratios (1:10 or 1:7.5), four terpene types (limonene, cineole, fenchone or citral) and two terpene concentrations (0.75% or 1.5%, w/v). They were characterized for drug entrapment efficiency (EE%), particle size (PS), zeta potential (ZP) and drug released percentages after 0.5h (Q0.5h) and 8h (Q8h). The optimum invasomes (I1, I2 and I4) were evaluated for morphology, drug-crystallinity, and ex-vivo drug flux. The variables influencing sonophoresis of the best achieved invasomal gel system (I2) were optimized including, ultrasound frequency (low, LFU or high, HFU), mode (pulsed or continuous), application period (10 min or 15 min) and duty cycle (50% or 100%). AGM pharmacokinetics were evaluated in rabbits following transdermal application of I2-LFU-C4 system, relative to AGM oral dispersion.Results: The superiority of I2 invasomes [comprising AGM and phosphatidylcholine (1:10) and limonene (1.5% w/v)] was statistically revealed with respect to EE% (78.6%), PS (313 nm), ZP (− 64 mV), Q0.5h (30.1%), Q8h (92%), flux (10.79 μg/cm2/h) and enhancement ratio (4.83). The optimum sonophoresis conditions involved application of LFU in the continuous mode for 15 min at a 100% duty cycle (I2-LFU-C4 system). The latter system showed significantly higher Cmax, and relative bioavailability (≈ 7.25 folds) and a similar Tmax (0.5 h).Conclusion: I2-LFU-C4 is a promising transdermal system for AGM.Keywords: agomelatine, invasomes, transdermal, sonophoresis, low frequency ultrasound
format	article
author	Tawfik MA Tadros MI Mohamed MI Nageeb El-Helaly S
author_facet	Tawfik MA Tadros MI Mohamed MI Nageeb El-Helaly S
author_sort	Tawfik MA
title	Low-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment
title_short	Low-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment
title_full	Low-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment
title_fullStr	Low-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment
title_full_unstemmed	Low-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment
title_sort	low-frequency versus high-frequency ultrasound-mediated transdermal delivery of agomelatine-loaded invasomes: development, optimization and in-vivo pharmacokinetic assessment
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/3dc5f1f12f694287a2e7cf7bf14c89a3
work_keys_str_mv	AT tawfikma lowfrequencyversushighfrequencyultrasoundmediatedtransdermaldeliveryofagomelatineloadedinvasomesdevelopmentoptimizationandinvivopharmacokineticassessment AT tadrosmi lowfrequencyversushighfrequencyultrasoundmediatedtransdermaldeliveryofagomelatineloadedinvasomesdevelopmentoptimizationandinvivopharmacokineticassessment AT mohamedmi lowfrequencyversushighfrequencyultrasoundmediatedtransdermaldeliveryofagomelatineloadedinvasomesdevelopmentoptimizationandinvivopharmacokineticassessment AT nageebelhelalys lowfrequencyversushighfrequencyultrasoundmediatedtransdermaldeliveryofagomelatineloadedinvasomesdevelopmentoptimizationandinvivopharmacokineticassessment
_version_	1718394741292269568

Low-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment

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