mPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus

Anan Yu,1,* Jieqiong Lv,1,* Fang Yuan,1 Zihua Xia,1 Kaiyan Fan,1 Gang Chen,1,2 Jialin Ren,1 Cuicui Lin,1 Shijie Wei,1,2 Fan Yang1,2 1Department of Pharmaceutics, 2Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, Guangdo...

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Autores principales:	Yu A, Lv J, Yuan F, Xia Z, Fan K, Chen G, Ren J, Lin C, Wei S, Yang F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Bioavailability epilepsy intranasal administration lamotrigine mixed micelle TPGS Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/923e727a12b840b6a08edf38485a8075
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spelling	oai:doaj.org-article:923e727a12b840b6a08edf38485a80752021-12-02T05:08:58ZmPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus1178-2013https://doaj.org/article/923e727a12b840b6a08edf38485a80752017-11-01T00:00:00Zhttps://www.dovepress.com/mpeg-platpgs-mixed-micelles-via-intranasal-administration-improved-the-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Anan Yu,1,* Jieqiong Lv,1,* Fang Yuan,1 Zihua Xia,1 Kaiyan Fan,1 Gang Chen,1,2 Jialin Ren,1 Cuicui Lin,1 Shijie Wei,1,2 Fan Yang1,2 1Department of Pharmaceutics, 2Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China *These authors contributed equally to this work Purpose: This study aimed to develop a novel methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelle drug delivery system to improve lamotrigine (LTG) distribution in the hippocampus.Methods: LTG-loaded mPEG-PLA/TPGS mixed micelles and LTG-loaded mPEG-PLA micelles were formulated, and their characteristics, particle size, surface morphology, and release behavior in vitro were researched. Then, a microdialysis sampling technique coupled with two validated chromatographic systems was developed for the continuous measurement of the protein-unbound form of LTG in the rat plasma and hippocampus after administering two kinds of micelles and LTG solution intranasally. Results: The drug loading and mean size of LTG-loaded micelles and LTG-loaded mixed micelles prepared with optimal formulation were 36.44%±0.14%, 39.28%±0.26%, 122.9, and 183.5 nm, respectively, with a core–shell structure. The cumulative release rate in vivo of LTG-loaded mixed micelles was 84.21% at 24 hours and showed more sustained release while that of LTG-loaded micelles was 80.61% at 6 hours. The Tmax and area under concentration-time curve from zero to time of last quantifiable concentration of LTG solution, LTG-loaded micelles, and LTG-loaded mixed micelles were 55, 35, and 15 minutes and about 5,384, 16,500, and 25,245 (min·µg)/L in the hippocampus, respectively.Conclusion: The results revealed that LTG-loaded mPEG-PLA/TPGS mixed micelles enhanced the absorption of LTG at the nasal cavity and reduced the efflux of LTG in the brain, suggesting that the function of TPGS inhibited P-glycoprotein and LTG-loaded mPEG-PLA/TPGS mixed micelles had the potential to overcome refractory epilepsy. Keywords: epilepsy, intranasal administration, lamotrigine, P-glycoprotein, blood brain barrier, TPGSYu ALv JYuan FXia ZFan KChen GRen JLin CWei SYang FDove Medical PressarticleBioavailabilityepilepsyintranasal administrationlamotriginemixed micelleTPGSMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 8353-8362 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bioavailability epilepsy intranasal administration lamotrigine mixed micelle TPGS Medicine (General) R5-920
spellingShingle	Bioavailability epilepsy intranasal administration lamotrigine mixed micelle TPGS Medicine (General) R5-920 Yu A Lv J Yuan F Xia Z Fan K Chen G Ren J Lin C Wei S Yang F mPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus
description	Anan Yu,1,* Jieqiong Lv,1,* Fang Yuan,1 Zihua Xia,1 Kaiyan Fan,1 Gang Chen,1,2 Jialin Ren,1 Cuicui Lin,1 Shijie Wei,1,2 Fan Yang1,2 1Department of Pharmaceutics, 2Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China *These authors contributed equally to this work Purpose: This study aimed to develop a novel methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelle drug delivery system to improve lamotrigine (LTG) distribution in the hippocampus.Methods: LTG-loaded mPEG-PLA/TPGS mixed micelles and LTG-loaded mPEG-PLA micelles were formulated, and their characteristics, particle size, surface morphology, and release behavior in vitro were researched. Then, a microdialysis sampling technique coupled with two validated chromatographic systems was developed for the continuous measurement of the protein-unbound form of LTG in the rat plasma and hippocampus after administering two kinds of micelles and LTG solution intranasally. Results: The drug loading and mean size of LTG-loaded micelles and LTG-loaded mixed micelles prepared with optimal formulation were 36.44%±0.14%, 39.28%±0.26%, 122.9, and 183.5 nm, respectively, with a core–shell structure. The cumulative release rate in vivo of LTG-loaded mixed micelles was 84.21% at 24 hours and showed more sustained release while that of LTG-loaded micelles was 80.61% at 6 hours. The Tmax and area under concentration-time curve from zero to time of last quantifiable concentration of LTG solution, LTG-loaded micelles, and LTG-loaded mixed micelles were 55, 35, and 15 minutes and about 5,384, 16,500, and 25,245 (min·µg)/L in the hippocampus, respectively.Conclusion: The results revealed that LTG-loaded mPEG-PLA/TPGS mixed micelles enhanced the absorption of LTG at the nasal cavity and reduced the efflux of LTG in the brain, suggesting that the function of TPGS inhibited P-glycoprotein and LTG-loaded mPEG-PLA/TPGS mixed micelles had the potential to overcome refractory epilepsy. Keywords: epilepsy, intranasal administration, lamotrigine, P-glycoprotein, blood brain barrier, TPGS
format	article
author	Yu A Lv J Yuan F Xia Z Fan K Chen G Ren J Lin C Wei S Yang F
author_facet	Yu A Lv J Yuan F Xia Z Fan K Chen G Ren J Lin C Wei S Yang F
author_sort	Yu A
title	mPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus
title_short	mPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus
title_full	mPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus
title_fullStr	mPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus
title_full_unstemmed	mPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus
title_sort	mpeg-pla/tpgs mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/923e727a12b840b6a08edf38485a8075
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mPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus

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