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A Novel Carbon Dots/Thermo-Sensitive In Situ Gel for a Composite Ocular Drug Delivery System: Characterization,Ex-Vivo Imaging,and In Vivo Evaluation
Authors:Lijie Wang  Hao Pan  Donghao Gu  Haowei Sun  Kai Chen  Guoxin Tan  Weisan Pan
Affiliation:1.Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China; (L.W.); (D.G.); (H.S.); (K.C.); (G.T.);2.College of Pharmacy, Liaoning University, Shenyang 110036, China;
Abstract:We developed a potential composite ocular drug delivery system for the topical administration of diclofenac sodium (DS). The novel carbon dot CDC-HP was synthesized by the pyrolysis of hyaluronic acid and carboxymethyl chitosan through a one-step hydrothermal method and then embedded in a thermosensitive in situ gel of poloxamer 407 and poloxamer 188 through swelling loading. The physicochemical characteristics of these carbon dots were investigated. The results of the in vitro release test showed that this composite ocular drug delivery system (DS-CDC-HP-Gel) exhibited sustained release for 12 h. The study of the ex vivo fluorescence distribution in ocular tissues showed that it could be used for bioimaging and tracing in ocular tissues and prolong precorneal retention. Elimination profiles in tears corresponded to the study of ex vivo fluorescence imaging. The area under the curve of DS in the aqueous humor in the DS-CDC-HP-Gel group was 3.45-fold that in the DS eye drops group, indicating a longer precorneal retention time. DS-CDC-HP with a positive charge and combined with a thermosensitive in situ gel might strengthen adherence to the corneal surface and prolong the ocular surface retention time to improve the bioavailability. This composite ocular delivery system possesses potential applications in ocular imaging and drug delivery.
Keywords:carbon dots  thermosensitive in situ gel  composite ocular drug delivery  pharmacokinetics
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