Primary Studies on Construction and Evaluation of Ion-Sensitive in situ Gel Loaded with Paeonol-Solid Lipid Nanoparticles for Intranasal Drug Delivery

Yue Sun,1 Lingjun Li,1 Huichao Xie,2 Yuzhen Wang,1 Shuang Gao,1 Li Zhang,1 Fumin Bo,1 Shanjing Yang,1 Anjie Feng1 1College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, People’s Republic of China; 2School of Pharmacy, Shenyang Pharmaceutical University, Sh...

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Autores principales:	Sun Y, Li L, Xie H, Wang Y, Gao S, Zhang L, Bo F, Yang S, Feng A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	paeonol in vitro metabolism solid lipid nanoparticles in situ gel nose-brain transport Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6422c7b3471741b19972e6b00d608b61
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spelling	oai:doaj.org-article:6422c7b3471741b19972e6b00d608b612021-12-02T12:09:46ZPrimary Studies on Construction and Evaluation of Ion-Sensitive in situ Gel Loaded with Paeonol-Solid Lipid Nanoparticles for Intranasal Drug Delivery1178-2013https://doaj.org/article/6422c7b3471741b19972e6b00d608b612020-05-01T00:00:00Zhttps://www.dovepress.com/primary-studies-on-construction-and-evaluation-of-ion-sensitive-in-sit-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yue Sun,1 Lingjun Li,1 Huichao Xie,2 Yuzhen Wang,1 Shuang Gao,1 Li Zhang,1 Fumin Bo,1 Shanjing Yang,1 Anjie Feng1 1College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, People’s Republic of China; 2School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of ChinaCorrespondence: Lingjun Li Email sdzyylilingjun@163.comBackground: Paeonol (PAE) is a potential central neuroprotective agent with poor water solubility and rapid metabolism in vivo. The key to improve the clinical application of PAE in the treatment of neurodegenerative diseases is to improve the brain delivery of it. The purpose of this study was to construct a paeonol-solid lipid nanoparticles-in situ gel (PAE-SLNs-ISG) drug delivery system based on nose-brain transport pathway.Materials and Methods: In this study, the stability of PAE in simulated biological samples was studied firstly in order to clarify the reasons for low oral bioavailability. Paeonol-solid lipid nanoparticles (PAE-SLNs) were prepared by high-temperature emulsification–low-temperature curing combined with ultrasound. The PAE-SLNs-ISG drug delivery system was constructed, and related formulation optimization, preparation characterization, cell evaluation and in vivo evaluation were performed.Results: The metabolic mechanism of PAE incubated in the liver microsomes metabolic system was in accordance with the first-order kinetics, and the half-life was 0.23 h. PAE-SLNs were polyhedral or spherical particles with good dispersion and the particle size was 166.79 nm ± 2.92 nm. PAE-SLNs-ISG solution was a Newtonian fluid with a viscosity of 44.36 mPa · S ± 2.89 mPa · S. The viscosity of PAE-SLNs-ISG gel was 1542.19 mPa · S ± 19.30 mPa · S, and the rheological evaluation showed that the gel was a non-Newtonian pseudoplastic fluid with shear thinning, thixotropy and yield value. The release mechanism of PAE from PAE-SLNs was drug diffusion; the release mechanism of PAE from PAE-SLNs-ISG was a synergistic effect of skeleton erosion and drug diffusion. The cell viabilities of PAE-SLNs and PAE-SLNs-ISG in the concentration range of 0.001 μg/mL to 10 μg/mL were higher than 90%, showing a low level of cytotoxicity. The geometric mean fluorescent intensities of RPMI 2650 cells incubated with fluorescein isothiocyanate-solid lipid nanoparticles (FITC-SLNs) for 1 h, 4 h and 6 h were 1841 ± 24, 2261 ± 27 and 2757 ± 22, respectively. Cyanine7 NHS ester-solid lipid nanoparticles-in situ gel (Cy7-SLNs-ISG) accumulated effectively in the brain area after administration through the olfactory area, and the fluorescence response was observed in olfactory bulb, cerebellum and striatum.Conclusion: SLNs-ISG nose-brain drug delivery system can effectively deliver SLNs to brain regions, and it is a potentially effective strategy to realize the brain region delivery of PAE.Keywords: paeonol, in vitro metabolism, solid lipid nanoparticles, in situ gel, nose-brain transportSun YLi LXie HWang YGao SZhang LBo FYang SFeng ADove Medical Pressarticlepaeonolin vitro metabolismsolid lipid nanoparticlesin situ gelnose-brain transportMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 3137-3160 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	paeonol in vitro metabolism solid lipid nanoparticles in situ gel nose-brain transport Medicine (General) R5-920
spellingShingle	paeonol in vitro metabolism solid lipid nanoparticles in situ gel nose-brain transport Medicine (General) R5-920 Sun Y Li L Xie H Wang Y Gao S Zhang L Bo F Yang S Feng A Primary Studies on Construction and Evaluation of Ion-Sensitive in situ Gel Loaded with Paeonol-Solid Lipid Nanoparticles for Intranasal Drug Delivery
description	Yue Sun,1 Lingjun Li,1 Huichao Xie,2 Yuzhen Wang,1 Shuang Gao,1 Li Zhang,1 Fumin Bo,1 Shanjing Yang,1 Anjie Feng1 1College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, People’s Republic of China; 2School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of ChinaCorrespondence: Lingjun Li Email sdzyylilingjun@163.comBackground: Paeonol (PAE) is a potential central neuroprotective agent with poor water solubility and rapid metabolism in vivo. The key to improve the clinical application of PAE in the treatment of neurodegenerative diseases is to improve the brain delivery of it. The purpose of this study was to construct a paeonol-solid lipid nanoparticles-in situ gel (PAE-SLNs-ISG) drug delivery system based on nose-brain transport pathway.Materials and Methods: In this study, the stability of PAE in simulated biological samples was studied firstly in order to clarify the reasons for low oral bioavailability. Paeonol-solid lipid nanoparticles (PAE-SLNs) were prepared by high-temperature emulsification–low-temperature curing combined with ultrasound. The PAE-SLNs-ISG drug delivery system was constructed, and related formulation optimization, preparation characterization, cell evaluation and in vivo evaluation were performed.Results: The metabolic mechanism of PAE incubated in the liver microsomes metabolic system was in accordance with the first-order kinetics, and the half-life was 0.23 h. PAE-SLNs were polyhedral or spherical particles with good dispersion and the particle size was 166.79 nm ± 2.92 nm. PAE-SLNs-ISG solution was a Newtonian fluid with a viscosity of 44.36 mPa · S ± 2.89 mPa · S. The viscosity of PAE-SLNs-ISG gel was 1542.19 mPa · S ± 19.30 mPa · S, and the rheological evaluation showed that the gel was a non-Newtonian pseudoplastic fluid with shear thinning, thixotropy and yield value. The release mechanism of PAE from PAE-SLNs was drug diffusion; the release mechanism of PAE from PAE-SLNs-ISG was a synergistic effect of skeleton erosion and drug diffusion. The cell viabilities of PAE-SLNs and PAE-SLNs-ISG in the concentration range of 0.001 μg/mL to 10 μg/mL were higher than 90%, showing a low level of cytotoxicity. The geometric mean fluorescent intensities of RPMI 2650 cells incubated with fluorescein isothiocyanate-solid lipid nanoparticles (FITC-SLNs) for 1 h, 4 h and 6 h were 1841 ± 24, 2261 ± 27 and 2757 ± 22, respectively. Cyanine7 NHS ester-solid lipid nanoparticles-in situ gel (Cy7-SLNs-ISG) accumulated effectively in the brain area after administration through the olfactory area, and the fluorescence response was observed in olfactory bulb, cerebellum and striatum.Conclusion: SLNs-ISG nose-brain drug delivery system can effectively deliver SLNs to brain regions, and it is a potentially effective strategy to realize the brain region delivery of PAE.Keywords: paeonol, in vitro metabolism, solid lipid nanoparticles, in situ gel, nose-brain transport
format	article
author	Sun Y Li L Xie H Wang Y Gao S Zhang L Bo F Yang S Feng A
author_facet	Sun Y Li L Xie H Wang Y Gao S Zhang L Bo F Yang S Feng A
author_sort	Sun Y
title	Primary Studies on Construction and Evaluation of Ion-Sensitive in situ Gel Loaded with Paeonol-Solid Lipid Nanoparticles for Intranasal Drug Delivery
title_short	Primary Studies on Construction and Evaluation of Ion-Sensitive in situ Gel Loaded with Paeonol-Solid Lipid Nanoparticles for Intranasal Drug Delivery
title_full	Primary Studies on Construction and Evaluation of Ion-Sensitive in situ Gel Loaded with Paeonol-Solid Lipid Nanoparticles for Intranasal Drug Delivery
title_fullStr	Primary Studies on Construction and Evaluation of Ion-Sensitive in situ Gel Loaded with Paeonol-Solid Lipid Nanoparticles for Intranasal Drug Delivery
title_full_unstemmed	Primary Studies on Construction and Evaluation of Ion-Sensitive in situ Gel Loaded with Paeonol-Solid Lipid Nanoparticles for Intranasal Drug Delivery
title_sort	primary studies on construction and evaluation of ion-sensitive in situ gel loaded with paeonol-solid lipid nanoparticles for intranasal drug delivery
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/6422c7b3471741b19972e6b00d608b61
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Primary Studies on Construction and Evaluation of Ion-Sensitive in situ Gel Loaded with Paeonol-Solid Lipid Nanoparticles for Intranasal Drug Delivery

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