Prolonged Release of Anti-inflammatory Diclofenac Sodium from  In Situ  Loaded Thermosensitive Chitosan Hydrogels for Localized Applications

Nga Hoang Nguyen Do; Ha Vu Le; Khoa Dang Nguyen; Anh Cam Ha

doi:10.22146/ijc.106833

Prolonged Release of Anti-inflammatory Diclofenac Sodium from In Situ Loaded Thermosensitive Chitosan Hydrogels for Localized Applications

https://doi.org/10.22146/ijc.106833

Nga Hoang Nguyen Do⁽¹⁾, Ha Vu Le⁽²⁾, Khoa Dang Nguyen⁽³⁾, Anh Cam Ha^(4*)

(1) Faculty of Chemical Engineering, Ho Chi Minh City University of Technology (HCMUT), 268 Ly Thuong Kiet Street, District 10, Ho Chi Minh City 740500, Vietnam; Vietnam National University Ho Chi Minh City, Linh Trung Ward, Thu Duc City, Ho Chi Minh City 721400, Vietnam
(2) Faculty of Chemical Engineering, Ho Chi Minh City University of Technology (HCMUT), 268 Ly Thuong Kiet Street, District 10, Ho Chi Minh City 740500, Vietnam; Vietnam National University Ho Chi Minh City, Linh Trung Ward, Thu Duc City, Ho Chi Minh City 721400, Vietnam
(3) Faculty of Chemical Engineering, Ho Chi Minh City University of Technology (HCMUT), 268 Ly Thuong Kiet Street, District 10, Ho Chi Minh City 740500, Vietnam; Vietnam National University Ho Chi Minh City, Linh Trung Ward, Thu Duc City, Ho Chi Minh City 721400, Vietnam
(4) Faculty of Chemical Engineering, Ho Chi Minh City University of Technology (HCMUT), 268 Ly Thuong Kiet Street, District 10, Ho Chi Minh City 740500, Vietnam; Vietnam National University Ho Chi Minh City, Linh Trung Ward, Thu Duc City, Ho Chi Minh City 721400, Vietnam
(*) Corresponding Author

Abstract

Previous work developed a thermosensitive hydrogel from chitosan (CS) and β-glycerophosphate (GP) loaded with diclofenac sodium (DIC) using a post-loading method. The hydrogel as a wound dressing exhibited burst release of DIC within 5 h, rendering it suitable for immediate anti-inflammatory treatment. For the first time, the in situ loading method has been applied to synthesize an injectable CS/GP hydrogel for prolonged DIC release. The optimal synthesis condition is at 1.0 w/v% CS (high molecular weight of 324 kDa) and 4.0 w/v% GP, yielding the hydrogel capable of sol-gel transition at 37 °C. The porous structure of the hydrogels is filled with DIC, ensuring efficient drug entrapment. The hydrogels demonstrate prolonged DIC release over 7 days, achieving a cumulative drug release (CDR) ranging from 62.39 to 80.51%. At an initial DIC loading of 3000 µg/mL, the hydrogel maintains a drug concentration above 10 µg/mL after 6 days of release. DIC release kinetics are temperature-dependent, with a higher CDR at 39 °C (simulating an inflammatory condition) than 37 °C (normal body temperature), and governed by drug diffusion and hydrogel network swelling. This study provides a novel approach for synthesizing an injectable temperature-responsive CS hydrogel for local anti-inflammatory DIC delivery.

Keywords

thermosensitive hydrogel; diclofenac sodium; in situ loading; characterization; release profile

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DOI: https://doi.org/10.22146/ijc.106833