Cargando…

Nanomicelle formulation for topical delivery of cyclosporine A into the cornea: in vitro mechanism and in vivo permeation evaluation

A stable topical ophthalmic cyclosporine A (CsA) formulation with good tolerance and high efficacy is still a desire in pharmaceutics and clinics. This article describes the preparation of CsA containing nanomicelles using a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCL-PVA-PEG)...

Descripción completa

Detalles Bibliográficos
Autores principales: Guo, Chuanlong, Zhang, Yan, Yang, Zhao, Li, Mengshuang, Li, Fengjie, Cui, Fenghua, Liu, Ting, Shi, Weiyun, Wu, Xianggen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549686/
http://dx.doi.org/10.1038/srep12968
_version_ 1782387348433010688
author Guo, Chuanlong
Zhang, Yan
Yang, Zhao
Li, Mengshuang
Li, Fengjie
Cui, Fenghua
Liu, Ting
Shi, Weiyun
Wu, Xianggen
author_facet Guo, Chuanlong
Zhang, Yan
Yang, Zhao
Li, Mengshuang
Li, Fengjie
Cui, Fenghua
Liu, Ting
Shi, Weiyun
Wu, Xianggen
author_sort Guo, Chuanlong
collection PubMed
description A stable topical ophthalmic cyclosporine A (CsA) formulation with good tolerance and high efficacy is still a desire in pharmaceutics and clinics. This article describes the preparation of CsA containing nanomicelles using a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCL-PVA-PEG) graft copolymer. Both the polymer itself and the CsA nanomicelles were evaluated for cytotoxicity and ocular irritation. The in vitro uptake and intracellular fate of nanomicelles were characterized. In vivo cornea permeation test performed with 0.5 mg/mL CsA containing nanomicelles, and compared with a commercially available CsA (10 mg/mL) oil-based ophthalmic solution. The CsA nanomicelle ophthalmic solution was simple to prepare and remained storage stable. PVCL-PVA-PEG had no cytotoxicity as its monomer solution, and as its micelle solution (IC(50)(48 h) = 14.02 mg/mL). CsA nanomicelles also had excellent ocular tolerance in rabbits. The use of nanomicelles significantly improved in vitro cellular uptake, apparently by an energy dependent intracellular endocytosis pathway that involved early endosomes, late endosomes, lysosomes, and ER. In vivo permeation showed that 0.5 mg/mL CsA nanomicelles delivered high levels of CsA into the cornea, when compared to the oil-based 10 mg/mL CsA ophthalmic solution. These findings indicated PVCL-PVA-PEG nanomicelles could be a promising topical delivery system for ocular administration of CsA.
format Online
Article
Text
id pubmed-4549686
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-45496862015-08-26 Nanomicelle formulation for topical delivery of cyclosporine A into the cornea: in vitro mechanism and in vivo permeation evaluation Guo, Chuanlong Zhang, Yan Yang, Zhao Li, Mengshuang Li, Fengjie Cui, Fenghua Liu, Ting Shi, Weiyun Wu, Xianggen Sci Rep Article A stable topical ophthalmic cyclosporine A (CsA) formulation with good tolerance and high efficacy is still a desire in pharmaceutics and clinics. This article describes the preparation of CsA containing nanomicelles using a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCL-PVA-PEG) graft copolymer. Both the polymer itself and the CsA nanomicelles were evaluated for cytotoxicity and ocular irritation. The in vitro uptake and intracellular fate of nanomicelles were characterized. In vivo cornea permeation test performed with 0.5 mg/mL CsA containing nanomicelles, and compared with a commercially available CsA (10 mg/mL) oil-based ophthalmic solution. The CsA nanomicelle ophthalmic solution was simple to prepare and remained storage stable. PVCL-PVA-PEG had no cytotoxicity as its monomer solution, and as its micelle solution (IC(50)(48 h) = 14.02 mg/mL). CsA nanomicelles also had excellent ocular tolerance in rabbits. The use of nanomicelles significantly improved in vitro cellular uptake, apparently by an energy dependent intracellular endocytosis pathway that involved early endosomes, late endosomes, lysosomes, and ER. In vivo permeation showed that 0.5 mg/mL CsA nanomicelles delivered high levels of CsA into the cornea, when compared to the oil-based 10 mg/mL CsA ophthalmic solution. These findings indicated PVCL-PVA-PEG nanomicelles could be a promising topical delivery system for ocular administration of CsA. Nature Publishing Group 2015-08-26 /pmc/articles/PMC4549686/ http://dx.doi.org/10.1038/srep12968 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Guo, Chuanlong
Zhang, Yan
Yang, Zhao
Li, Mengshuang
Li, Fengjie
Cui, Fenghua
Liu, Ting
Shi, Weiyun
Wu, Xianggen
Nanomicelle formulation for topical delivery of cyclosporine A into the cornea: in vitro mechanism and in vivo permeation evaluation
title Nanomicelle formulation for topical delivery of cyclosporine A into the cornea: in vitro mechanism and in vivo permeation evaluation
title_full Nanomicelle formulation for topical delivery of cyclosporine A into the cornea: in vitro mechanism and in vivo permeation evaluation
title_fullStr Nanomicelle formulation for topical delivery of cyclosporine A into the cornea: in vitro mechanism and in vivo permeation evaluation
title_full_unstemmed Nanomicelle formulation for topical delivery of cyclosporine A into the cornea: in vitro mechanism and in vivo permeation evaluation
title_short Nanomicelle formulation for topical delivery of cyclosporine A into the cornea: in vitro mechanism and in vivo permeation evaluation
title_sort nanomicelle formulation for topical delivery of cyclosporine a into the cornea: in vitro mechanism and in vivo permeation evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549686/
http://dx.doi.org/10.1038/srep12968
work_keys_str_mv AT guochuanlong nanomicelleformulationfortopicaldeliveryofcyclosporineaintothecorneainvitromechanismandinvivopermeationevaluation
AT zhangyan nanomicelleformulationfortopicaldeliveryofcyclosporineaintothecorneainvitromechanismandinvivopermeationevaluation
AT yangzhao nanomicelleformulationfortopicaldeliveryofcyclosporineaintothecorneainvitromechanismandinvivopermeationevaluation
AT limengshuang nanomicelleformulationfortopicaldeliveryofcyclosporineaintothecorneainvitromechanismandinvivopermeationevaluation
AT lifengjie nanomicelleformulationfortopicaldeliveryofcyclosporineaintothecorneainvitromechanismandinvivopermeationevaluation
AT cuifenghua nanomicelleformulationfortopicaldeliveryofcyclosporineaintothecorneainvitromechanismandinvivopermeationevaluation
AT liuting nanomicelleformulationfortopicaldeliveryofcyclosporineaintothecorneainvitromechanismandinvivopermeationevaluation
AT shiweiyun nanomicelleformulationfortopicaldeliveryofcyclosporineaintothecorneainvitromechanismandinvivopermeationevaluation
AT wuxianggen nanomicelleformulationfortopicaldeliveryofcyclosporineaintothecorneainvitromechanismandinvivopermeationevaluation