Enhanced and sustained topical ocular delivery of cyclosporine A in thermosensitive hyaluronic acid-based in situ forming microgels

Yijun Wu, Jing Yao, Jianping Zhou, Fatima Zohra Dahmani State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang, Nanjing, People’s Republic of China Abstract: For nearly a decade, thermoresponsive ophthalmic in situ gels have been recognized as an interesti...

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Autores principales: Wu Y, Yao J, Zhou J, Dahmani FZ
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Publicado: Dove Medical Press 2013
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spelling oai:doaj.org-article:dd86c4efcdbf4c82b0210b560d22e4182021-12-02T07:22:52ZEnhanced and sustained topical ocular delivery of cyclosporine A in thermosensitive hyaluronic acid-based in situ forming microgels1176-91141178-2013https://doaj.org/article/dd86c4efcdbf4c82b0210b560d22e4182013-09-01T00:00:00Zhttp://www.dovepress.com/enhanced-and-sustained-topical-ocular-delivery-of-cyclosporine-a-in-th-a14429https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yijun Wu, Jing Yao, Jianping Zhou, Fatima Zohra Dahmani State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang, Nanjing, People’s Republic of China Abstract: For nearly a decade, thermoresponsive ophthalmic in situ gels have been recognized as an interesting and promising ocular topical delivery vehicle for lipophilic drugs. In this study, a series of thermosensitive copolymers, hyaluronic acid-g-poly(N-isopropylacrylamide) (HA-g-PNIPAAm), was synthesized, by coupling carboxylic end-capped PNIPAAm to aminated hyaluronic acid through amide bond linkages, and was used as a potential carrier for the topical ocular administration of cyclosporine A (CyA). The lower critical solution temperature of HA-g-PNIPAAm59 in aqueous solutions was measured as 32.7°C, which was not significantly affected by the polymer concentration. Moreover, HA-g-PNIPAAm59 microgels showed a high drug loading efficiency (73.92%) and a controlled release profile that are necessary for biomedical application. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) observations showed that HA-g-PNIPAAm microgels were spherical in shape with homogeneous size. Based on the result of the eye irritation test, the HA-g-PNIPAAm microgels formulation was shown to be safe and nonirritant for rabbit eyes. In addition, HA-g-PNIPAAm microgels achieved significantly higher CyA concentration levels in rabbit corneas (1455.8 ng/g of tissue) than both castor oil formulation and commercial CyA eye drops. Therefore, these newly described thermoresponsive HA-g-PNIPAAm microgels demonstrated attractive properties to serve as pharmaceutical delivery vehicles for a variety of ophthalmic applications. Keywords: thermosensitive microgels, ophthalmic drug delivery, hyaluronic acid, cyclosporine AWu YYao JZhou JDahmani FZDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss Issue 1, Pp 3587-3601 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Wu Y
Yao J
Zhou J
Dahmani FZ
Enhanced and sustained topical ocular delivery of cyclosporine A in thermosensitive hyaluronic acid-based in situ forming microgels
description Yijun Wu, Jing Yao, Jianping Zhou, Fatima Zohra Dahmani State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang, Nanjing, People’s Republic of China Abstract: For nearly a decade, thermoresponsive ophthalmic in situ gels have been recognized as an interesting and promising ocular topical delivery vehicle for lipophilic drugs. In this study, a series of thermosensitive copolymers, hyaluronic acid-g-poly(N-isopropylacrylamide) (HA-g-PNIPAAm), was synthesized, by coupling carboxylic end-capped PNIPAAm to aminated hyaluronic acid through amide bond linkages, and was used as a potential carrier for the topical ocular administration of cyclosporine A (CyA). The lower critical solution temperature of HA-g-PNIPAAm59 in aqueous solutions was measured as 32.7°C, which was not significantly affected by the polymer concentration. Moreover, HA-g-PNIPAAm59 microgels showed a high drug loading efficiency (73.92%) and a controlled release profile that are necessary for biomedical application. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) observations showed that HA-g-PNIPAAm microgels were spherical in shape with homogeneous size. Based on the result of the eye irritation test, the HA-g-PNIPAAm microgels formulation was shown to be safe and nonirritant for rabbit eyes. In addition, HA-g-PNIPAAm microgels achieved significantly higher CyA concentration levels in rabbit corneas (1455.8 ng/g of tissue) than both castor oil formulation and commercial CyA eye drops. Therefore, these newly described thermoresponsive HA-g-PNIPAAm microgels demonstrated attractive properties to serve as pharmaceutical delivery vehicles for a variety of ophthalmic applications. Keywords: thermosensitive microgels, ophthalmic drug delivery, hyaluronic acid, cyclosporine A
format article
author Wu Y
Yao J
Zhou J
Dahmani FZ
author_facet Wu Y
Yao J
Zhou J
Dahmani FZ
author_sort Wu Y
title Enhanced and sustained topical ocular delivery of cyclosporine A in thermosensitive hyaluronic acid-based in situ forming microgels
title_short Enhanced and sustained topical ocular delivery of cyclosporine A in thermosensitive hyaluronic acid-based in situ forming microgels
title_full Enhanced and sustained topical ocular delivery of cyclosporine A in thermosensitive hyaluronic acid-based in situ forming microgels
title_fullStr Enhanced and sustained topical ocular delivery of cyclosporine A in thermosensitive hyaluronic acid-based in situ forming microgels
title_full_unstemmed Enhanced and sustained topical ocular delivery of cyclosporine A in thermosensitive hyaluronic acid-based in situ forming microgels
title_sort enhanced and sustained topical ocular delivery of cyclosporine a in thermosensitive hyaluronic acid-based in situ forming microgels
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/dd86c4efcdbf4c82b0210b560d22e418
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AT yaoj enhancedandsustainedtopicaloculardeliveryofcyclosporineainthermosensitivehyaluronicacidbasedinsituformingmicrogels
AT zhouj enhancedandsustainedtopicaloculardeliveryofcyclosporineainthermosensitivehyaluronicacidbasedinsituformingmicrogels
AT dahmanifz enhancedandsustainedtopicaloculardeliveryofcyclosporineainthermosensitivehyaluronicacidbasedinsituformingmicrogels
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