Novel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies

Jialu Wang,1 Fang Zhao,1 Rui Liu,1 Jingjing Chen,1 Qinghua Zhang,1 Ruijuan Lao,1 Ze Wang,1 Xin Jin,2 Changxiao Liu3 1School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Nankai District, 2Department of Pharmacology, Logistics University of Chinese People’s...

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Autores principales:	Wang J, Zhao F, Liu R, Chen J, Zhang Q, Lao R, Wang Z, Jin X, Liu C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Ocular delivery Microdialysis Molecular dynamics model Pharmacokinetic Preocular retention time Cationic lipid nanoparticle Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8af9a0536ec6437eafa4c1c01b12895b
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spelling	oai:doaj.org-article:8af9a0536ec6437eafa4c1c01b12895b2021-12-02T07:46:32ZNovel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies1178-2013https://doaj.org/article/8af9a0536ec6437eafa4c1c01b12895b2017-11-01T00:00:00Zhttps://www.dovepress.com/novel-cationic-lipid-nanoparticles-as-an-ophthalmic-delivery-system-fo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jialu Wang,1 Fang Zhao,1 Rui Liu,1 Jingjing Chen,1 Qinghua Zhang,1 Ruijuan Lao,1 Ze Wang,1 Xin Jin,2 Changxiao Liu3 1School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Nankai District, 2Department of Pharmacology, Logistics University of Chinese People’s Armed Police Force, Dongli District, 3State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Nankai District, Tianjin, China Abstract: The purpose of this study was to prepare, optimize, and characterize a cationic lipid nanoparticle (CLN) system containing multicomponent drugs using a molecular dynamics model as a novel method of evaluating formulations. Puerarin (PUE) and scutellarin (SCU) were used as model drugs. CLNs were successfully prepared using melt-emulsion ultrasonication and low temperature-solidification technique. The properties of CLNs such as morphology, particle size, zeta potential, entrapment efficiency (EE), drug loading (DL), and drug release behavior were investigated. The CLNs were evaluated by corneal permeation, preocular retention time, and pharmacokinetics in the aqueous humor. Additionally, a molecular dynamics model was used to evaluate the formulation. Electron microscopy results showed that the nanoparticles were approximately spherical in shape. The EE (%) and DL (%) values of PUE and SCU in the optimal formulation were 56.60±3.73, 72.31±1.96 and 1.68±0.17, 2.44±1.14, respectively. The pharmacokinetic study in the aqueous humor showed that compared with the PUE and SCU solution, the area under the concentration–time curve (AUC) value of PUE was enhanced by 2.33-fold for PUE-SCU CLNs (p<0.01), and the SCU AUC was enhanced by 2.32-fold (p<0.01). In the molecular dynamics model, PUE and SCU passed through the POPC bilayer, with an obvious difference in the free energy well depth. It was found that the maximum free energy required for PUE and SCU transmembrane movement was ~15 and 88 kJ·mol-1, respectively. These findings indicated that compared with SCU, PUE easily passed through the membrane. The diffusion coefficient for PUE and SCU were 4.1×10-3±0.0027 and 1.0×10-3±0.0006 e-5cm2·s-1, respectively. Data from the molecular dynamics model were consistent with the experimental data. All data indicated that CLNs have a great potential for ocular administration and can be used as an ocular delivery system for multicomponent drugs. Moreover, the molecular dynamics model can also be used as a novel method for evaluating formulations. Keywords: cationic lipid nanoparticle, molecular dynamics model, microdialysis, pharmacokinetic, preocular retention time, ocular deliveryWang JZhao FLiu RChen JZhang QLao RWang ZJin XLiu CDove Medical PressarticleOcular deliveryMicrodialysisMolecular dynamics modelPharmacokineticPreocular retention timeCationic lipid nanoparticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 8115-8127 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ocular delivery Microdialysis Molecular dynamics model Pharmacokinetic Preocular retention time Cationic lipid nanoparticle Medicine (General) R5-920
spellingShingle	Ocular delivery Microdialysis Molecular dynamics model Pharmacokinetic Preocular retention time Cationic lipid nanoparticle Medicine (General) R5-920 Wang J Zhao F Liu R Chen J Zhang Q Lao R Wang Z Jin X Liu C Novel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies
description	Jialu Wang,1 Fang Zhao,1 Rui Liu,1 Jingjing Chen,1 Qinghua Zhang,1 Ruijuan Lao,1 Ze Wang,1 Xin Jin,2 Changxiao Liu3 1School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Nankai District, 2Department of Pharmacology, Logistics University of Chinese People’s Armed Police Force, Dongli District, 3State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Nankai District, Tianjin, China Abstract: The purpose of this study was to prepare, optimize, and characterize a cationic lipid nanoparticle (CLN) system containing multicomponent drugs using a molecular dynamics model as a novel method of evaluating formulations. Puerarin (PUE) and scutellarin (SCU) were used as model drugs. CLNs were successfully prepared using melt-emulsion ultrasonication and low temperature-solidification technique. The properties of CLNs such as morphology, particle size, zeta potential, entrapment efficiency (EE), drug loading (DL), and drug release behavior were investigated. The CLNs were evaluated by corneal permeation, preocular retention time, and pharmacokinetics in the aqueous humor. Additionally, a molecular dynamics model was used to evaluate the formulation. Electron microscopy results showed that the nanoparticles were approximately spherical in shape. The EE (%) and DL (%) values of PUE and SCU in the optimal formulation were 56.60±3.73, 72.31±1.96 and 1.68±0.17, 2.44±1.14, respectively. The pharmacokinetic study in the aqueous humor showed that compared with the PUE and SCU solution, the area under the concentration–time curve (AUC) value of PUE was enhanced by 2.33-fold for PUE-SCU CLNs (p<0.01), and the SCU AUC was enhanced by 2.32-fold (p<0.01). In the molecular dynamics model, PUE and SCU passed through the POPC bilayer, with an obvious difference in the free energy well depth. It was found that the maximum free energy required for PUE and SCU transmembrane movement was ~15 and 88 kJ·mol-1, respectively. These findings indicated that compared with SCU, PUE easily passed through the membrane. The diffusion coefficient for PUE and SCU were 4.1×10-3±0.0027 and 1.0×10-3±0.0006 e-5cm2·s-1, respectively. Data from the molecular dynamics model were consistent with the experimental data. All data indicated that CLNs have a great potential for ocular administration and can be used as an ocular delivery system for multicomponent drugs. Moreover, the molecular dynamics model can also be used as a novel method for evaluating formulations. Keywords: cationic lipid nanoparticle, molecular dynamics model, microdialysis, pharmacokinetic, preocular retention time, ocular delivery
format	article
author	Wang J Zhao F Liu R Chen J Zhang Q Lao R Wang Z Jin X Liu C
author_facet	Wang J Zhao F Liu R Chen J Zhang Q Lao R Wang Z Jin X Liu C
author_sort	Wang J
title	Novel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies
title_short	Novel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies
title_full	Novel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies
title_fullStr	Novel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies
title_full_unstemmed	Novel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies
title_sort	novel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/8af9a0536ec6437eafa4c1c01b12895b
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Novel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies

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