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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Dove Medical Press
2013
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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) |
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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 |
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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 |
work_keys_str_mv |
AT wuy enhancedandsustainedtopicaloculardeliveryofcyclosporineainthermosensitivehyaluronicacidbasedinsituformingmicrogels AT yaoj enhancedandsustainedtopicaloculardeliveryofcyclosporineainthermosensitivehyaluronicacidbasedinsituformingmicrogels AT zhouj enhancedandsustainedtopicaloculardeliveryofcyclosporineainthermosensitivehyaluronicacidbasedinsituformingmicrogels AT dahmanifz enhancedandsustainedtopicaloculardeliveryofcyclosporineainthermosensitivehyaluronicacidbasedinsituformingmicrogels |
_version_ |
1718399485337403392 |