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Oral delivery of lycopene-loaded microemulsion for brain-targeting: preparation, characterization, pharmacokinetic evaluation and tissue distribution

Lycopene is considered as a promising neuroprotector with multiple bioactivities, while its therapeutic use in neurological disorders is restricted due to low solubility, instability and limited bioavailability. Our work aimed to develop lycopene-loaded microemulsion (LME) and investigate its potent...

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Autores principales: Guo, Yunliang, Mao, Xuyan, Zhang, Jing, Sun, Peng, Wang, Haiyang, Zhang, Yue, Ma, Yingjuan, Xu, Song, Lv, Renjun, Liu, Xueping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882477/
https://www.ncbi.nlm.nih.gov/pubmed/31738085
http://dx.doi.org/10.1080/10717544.2019.1689312
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author Guo, Yunliang
Mao, Xuyan
Zhang, Jing
Sun, Peng
Wang, Haiyang
Zhang, Yue
Ma, Yingjuan
Xu, Song
Lv, Renjun
Liu, Xueping
author_facet Guo, Yunliang
Mao, Xuyan
Zhang, Jing
Sun, Peng
Wang, Haiyang
Zhang, Yue
Ma, Yingjuan
Xu, Song
Lv, Renjun
Liu, Xueping
author_sort Guo, Yunliang
collection PubMed
description Lycopene is considered as a promising neuroprotector with multiple bioactivities, while its therapeutic use in neurological disorders is restricted due to low solubility, instability and limited bioavailability. Our work aimed to develop lycopene-loaded microemulsion (LME) and investigate its potentials in improving bioavailability and brain-targeting efficiency following oral administration. The blank microemulsion (ME) excipients were selected based on orthogonal design and pseudo-ternary phase diagrams, and LME was prepared using the water titration method and characterized in terms of stability, droplet size distribution, zeta potential, shape and lycopene content. The optimized LME encompassed lycopene, (R)-(+)-limonene, Tween 80, Transcutol HP and water and lycopene content was 463.03 ± 8.96 µg/mL. This novel formulation displayed transparent appearance and satisfactory physical and chemical stabilities. It was spherical and uniform in morphology with an average droplet size of 12.61 ± 0.46 nm and a polydispersity index (PDI) of 0.086 ± 0.028. The pharmacokinetics and tissue distributions of optimized LME were evaluated in rats and mice, respectively. The pharmacokinetic study revealed a dramatic 2.10-fold enhancement of relative bioavailability with LME against the control lycopene dissolved in olive oil (LOO) dosage form in rats. Moreover, LME showed a preferential targeting distribution of lycopene toward brain in mice, with the value of drug targeting index (DTI) up to 3.45. In conclusion, the optimized LME system demonstrated excellent physicochemical properties, enhanced oral bioavailability and superior brain-targeting capability. These findings provide a basis for the applications of ME-based strategy in brain-targeted delivery via oral route, especially for poorly water-soluble drugs.
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spelling pubmed-68824772019-12-09 Oral delivery of lycopene-loaded microemulsion for brain-targeting: preparation, characterization, pharmacokinetic evaluation and tissue distribution Guo, Yunliang Mao, Xuyan Zhang, Jing Sun, Peng Wang, Haiyang Zhang, Yue Ma, Yingjuan Xu, Song Lv, Renjun Liu, Xueping Drug Deliv Research Article Lycopene is considered as a promising neuroprotector with multiple bioactivities, while its therapeutic use in neurological disorders is restricted due to low solubility, instability and limited bioavailability. Our work aimed to develop lycopene-loaded microemulsion (LME) and investigate its potentials in improving bioavailability and brain-targeting efficiency following oral administration. The blank microemulsion (ME) excipients were selected based on orthogonal design and pseudo-ternary phase diagrams, and LME was prepared using the water titration method and characterized in terms of stability, droplet size distribution, zeta potential, shape and lycopene content. The optimized LME encompassed lycopene, (R)-(+)-limonene, Tween 80, Transcutol HP and water and lycopene content was 463.03 ± 8.96 µg/mL. This novel formulation displayed transparent appearance and satisfactory physical and chemical stabilities. It was spherical and uniform in morphology with an average droplet size of 12.61 ± 0.46 nm and a polydispersity index (PDI) of 0.086 ± 0.028. The pharmacokinetics and tissue distributions of optimized LME were evaluated in rats and mice, respectively. The pharmacokinetic study revealed a dramatic 2.10-fold enhancement of relative bioavailability with LME against the control lycopene dissolved in olive oil (LOO) dosage form in rats. Moreover, LME showed a preferential targeting distribution of lycopene toward brain in mice, with the value of drug targeting index (DTI) up to 3.45. In conclusion, the optimized LME system demonstrated excellent physicochemical properties, enhanced oral bioavailability and superior brain-targeting capability. These findings provide a basis for the applications of ME-based strategy in brain-targeted delivery via oral route, especially for poorly water-soluble drugs. Taylor & Francis 2019-11-18 /pmc/articles/PMC6882477/ /pubmed/31738085 http://dx.doi.org/10.1080/10717544.2019.1689312 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Guo, Yunliang
Mao, Xuyan
Zhang, Jing
Sun, Peng
Wang, Haiyang
Zhang, Yue
Ma, Yingjuan
Xu, Song
Lv, Renjun
Liu, Xueping
Oral delivery of lycopene-loaded microemulsion for brain-targeting: preparation, characterization, pharmacokinetic evaluation and tissue distribution
title Oral delivery of lycopene-loaded microemulsion for brain-targeting: preparation, characterization, pharmacokinetic evaluation and tissue distribution
title_full Oral delivery of lycopene-loaded microemulsion for brain-targeting: preparation, characterization, pharmacokinetic evaluation and tissue distribution
title_fullStr Oral delivery of lycopene-loaded microemulsion for brain-targeting: preparation, characterization, pharmacokinetic evaluation and tissue distribution
title_full_unstemmed Oral delivery of lycopene-loaded microemulsion for brain-targeting: preparation, characterization, pharmacokinetic evaluation and tissue distribution
title_short Oral delivery of lycopene-loaded microemulsion for brain-targeting: preparation, characterization, pharmacokinetic evaluation and tissue distribution
title_sort oral delivery of lycopene-loaded microemulsion for brain-targeting: preparation, characterization, pharmacokinetic evaluation and tissue distribution
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882477/
https://www.ncbi.nlm.nih.gov/pubmed/31738085
http://dx.doi.org/10.1080/10717544.2019.1689312
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