The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route

Yueyao Jiang, Chenqi Liu, Wanchen Zhai, Ning Zhuang, Tengfei Han, Zhiying Ding School of Pharmaceutical Sciences, Jilin University, Changchun 130021, People’s Republic of ChinaCorrespondence: Zhiying DingSchool of Pharmaceutical Sciences, Jilin University, Changchun 130021, People&rsqu...

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Autores principales:	Jiang Y, Liu C, Zhai W, Zhuang N, Han T, Ding Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	nanoemulsion lactoferrin brain targeting intranasal delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9146725e9ca8427daabd6888dc5343d1
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spelling	oai:doaj.org-article:9146725e9ca8427daabd6888dc5343d12021-12-02T04:38:35ZThe Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route1178-2013https://doaj.org/article/9146725e9ca8427daabd6888dc5343d12019-11-01T00:00:00Zhttps://www.dovepress.com/the-optimization-design-of-lactoferrin-loaded-hupa-nanoemulsion-for-ta-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yueyao Jiang, Chenqi Liu, Wanchen Zhai, Ning Zhuang, Tengfei Han, Zhiying Ding School of Pharmaceutical Sciences, Jilin University, Changchun 130021, People’s Republic of ChinaCorrespondence: Zhiying DingSchool of Pharmaceutical Sciences, Jilin University, Changchun 130021, People’s Republic of ChinaTel +8613843180286Email dzy@jlu.edu.cnBackground: Huperzine A (HupA) is a selective acetylcholinesterase inhibitor used to treat Alzheimer’s disease. The existing dosage of HupA lacks brain selectivity and can cause serious side effects in the gastrointestinal and peripheral cholinergic systems.Purpose: The aim of this study was to develop and characterize a HupA nanoemulsion (NE) and a targeted HupA-NE modified with lactoferrin (Lf) for intranasal administration.Methods: The NE was formulated using pseudo-ternary phase diagrams and optimized with response surface methodology. Particle size distribution and zeta potential were evaluated, and transmission electron microscopy was performed. We investigated the transport mechanisms of HupA-NEs into hCMEC/D3 cells, an in vitro model of the blood-brain barrier. HupA-NE, Lf-HupA-NE, and HupA solution were intranasally administered to rats to investigate the brain-targeting effects of these formulations. A drug targeting index (DTI) was calculated to determine brain-targeting efficiency.Results: Optimized HupA-NE had a particle size of 15.24±0.67 nm, polydispersity index (PDI) of 0.128±0.025, and zeta potential of −4.48±0.97 mV. The composition of the optimized HupA-NE was 3.00% isopropyl myristate (IPM), 3.81% Capryol 90, and 40% Cremophor EL + Labrasol. NEs, particularly Lf-HupA-NE, were taken up into hCMEC/D3 cells to a greater extent than pure drug alone. Western blot analysis showed that hCMEC/D3 cells contained P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance associated protein 1 (MRP1) transporters. The likely mechanisms resulting in higher NE transport to the brain were uptake by specific transporters and transcytosis. In vivo, intranasal Lf-HupA-NE significantly enhanced drug delivery to the brain compared to HupA-NE, which was confirmed by differences in pharmacokinetic parameters. The DTI of Lf-HupA-NE (3.2±0.75) demonstrated brain targeting, and the area under the curve for Lf-HupA-NE was significantly higher than that for HupA-NE.Conclusion: Lf-HupA-NE is a promising nasal drug delivery carrier for facilitating delivery of HupA to the central nervous system.Keywords: nanoemulsion, lactoferrin, brain targeting, intranasal delivery  Jiang YLiu CZhai WZhuang NHan TDing ZDove Medical Pressarticlenanoemulsionlactoferrinbrain targetingintranasal deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 9217-9234 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanoemulsion lactoferrin brain targeting intranasal delivery Medicine (General) R5-920
spellingShingle	nanoemulsion lactoferrin brain targeting intranasal delivery Medicine (General) R5-920 Jiang Y Liu C Zhai W Zhuang N Han T Ding Z The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route
description	Yueyao Jiang, Chenqi Liu, Wanchen Zhai, Ning Zhuang, Tengfei Han, Zhiying Ding School of Pharmaceutical Sciences, Jilin University, Changchun 130021, People’s Republic of ChinaCorrespondence: Zhiying DingSchool of Pharmaceutical Sciences, Jilin University, Changchun 130021, People’s Republic of ChinaTel +8613843180286Email dzy@jlu.edu.cnBackground: Huperzine A (HupA) is a selective acetylcholinesterase inhibitor used to treat Alzheimer’s disease. The existing dosage of HupA lacks brain selectivity and can cause serious side effects in the gastrointestinal and peripheral cholinergic systems.Purpose: The aim of this study was to develop and characterize a HupA nanoemulsion (NE) and a targeted HupA-NE modified with lactoferrin (Lf) for intranasal administration.Methods: The NE was formulated using pseudo-ternary phase diagrams and optimized with response surface methodology. Particle size distribution and zeta potential were evaluated, and transmission electron microscopy was performed. We investigated the transport mechanisms of HupA-NEs into hCMEC/D3 cells, an in vitro model of the blood-brain barrier. HupA-NE, Lf-HupA-NE, and HupA solution were intranasally administered to rats to investigate the brain-targeting effects of these formulations. A drug targeting index (DTI) was calculated to determine brain-targeting efficiency.Results: Optimized HupA-NE had a particle size of 15.24±0.67 nm, polydispersity index (PDI) of 0.128±0.025, and zeta potential of −4.48±0.97 mV. The composition of the optimized HupA-NE was 3.00% isopropyl myristate (IPM), 3.81% Capryol 90, and 40% Cremophor EL + Labrasol. NEs, particularly Lf-HupA-NE, were taken up into hCMEC/D3 cells to a greater extent than pure drug alone. Western blot analysis showed that hCMEC/D3 cells contained P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance associated protein 1 (MRP1) transporters. The likely mechanisms resulting in higher NE transport to the brain were uptake by specific transporters and transcytosis. In vivo, intranasal Lf-HupA-NE significantly enhanced drug delivery to the brain compared to HupA-NE, which was confirmed by differences in pharmacokinetic parameters. The DTI of Lf-HupA-NE (3.2±0.75) demonstrated brain targeting, and the area under the curve for Lf-HupA-NE was significantly higher than that for HupA-NE.Conclusion: Lf-HupA-NE is a promising nasal drug delivery carrier for facilitating delivery of HupA to the central nervous system.Keywords: nanoemulsion, lactoferrin, brain targeting, intranasal delivery
format	article
author	Jiang Y Liu C Zhai W Zhuang N Han T Ding Z
author_facet	Jiang Y Liu C Zhai W Zhuang N Han T Ding Z
author_sort	Jiang Y
title	The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route
title_short	The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route
title_full	The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route
title_fullStr	The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route
title_full_unstemmed	The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route
title_sort	optimization design of lactoferrin loaded hupa nanoemulsion for targeted drug transport via intranasal route
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/9146725e9ca8427daabd6888dc5343d1
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The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route

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