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

Authors Wu Y, Yao J, Zhou J, Dahmani FZ

Received 4 May 2013

Accepted for publication 9 July 2013

Published 20 September 2013 Volume 2013:8(1) Pages 3587—3601

DOI https://doi.org/10.2147/IJN.S47665

Checked for plagiarism Yes

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Peer reviewer comments 3

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

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Erratum

Iancu C, Mocan L

International Journal of Nanomedicine 2011, 6:2543-2544

Published Date: 21 October 2011