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Thermo-responsive Chitosan/β-glycerophosphate hydrogels directly post-loading anti-inflammatory diclofenac sodium

  • Original Paper: Sol-gel and hybrid materials for biological and health (medical) applications
  • Published:
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Abstract

In this study, diclofenac sodium (DS) is post-loaded directly into thermo-sensitive hydrogels fabricated from chitosan and β-glycerophosphate (GP) for temperature-controlled-release application at the inflammatory sites. Experiments analyzing the effect of GP concentration and simulated physiological temperature show that the hydrogels have a compatible heat-sensitive response through sol-gel and swelling behaviors. The hydrogels are soluble at 25 °C and rapidly gel above 37 °C with a decrease in the gelation time from 4 to 1 min when the temperature rises to 41 °C. Specific surface area, pore size, and pore volume of developed chitosan hydrogels are respectively 16.91–34.62 m2/g, 4.16–4.61 nm, and 0.08–0.28 cm3/g. Moreover, all hydrogels exhibit adaptive swelling to temperature changes as evidenced by the increase in equilibrium swelling ratio from 18.4–66.0% (25 °C) to 34.8–88.5% (37 °C) and 56.0–108.4% (39 °C). In terms of DS delivery, the highest loading capacity of the developed hydrogel is achieved at 8.81 mg/g with the GP content of 25 w/v%, the initial drug concentration of 2000 µg/ml, and the drug dissolution solvent being water, indicating the 23.8 times higher DS loading capacity compared with co-crosslinked chitosan/GP/genipin hydrogels in the previous work. About 87 and 95% of the loaded DS amount is released from the prepared chitosan hydrogels after 5 h at 37 and 39 °C correspondingly. The findings demonstrate that the ability to carry and release the anti-inflammatory DS of the thermo-sensitive chitosan hydrogels is significantly influenced by many subjective (composition) and objective (media temperature, initial drug concentration, and drug dissolution solvent) factors which can be adjusted to monitor the DS delivery at the right time and the right dose as required.

Graphical Abstract

Highlights

  • Diclofenac sodium is directly post-loaded into thermo-sensitive chitosan hydrogel.

  • The hydrogel is soluble at 25 °C and rapidly becomes gel at 39 °C in 4 min.

  • The highest swelling ratio of the hydrogel is 108.4% at 39 °C.

  • The maximum drug loading of the hydrogel is 8.81 mg/g.

  • 87% and 95% of drug-loaded is released after 5 h at 37 °C and 39 °C, respectively.

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Acknowledgements

NHND was funded by Vingroup JSC and supported by the Master, PhD Scholarship Programme of Vingroup Innovation Foundation (VINIF), Institute of Big Data, code VINIF.2021.TS.056. We also acknowledge the support of time and facilities from Ho Chi Minh City University of Technology (HCMUT), VNU-HCM for this study.

Author contributions

NHND: Investigation, Formal analysis, Writing - original draft, Validation; THP: Methodology, Characterization; PKL: Validation, Writing - review & editing; ACH: Conceptualization, Visualization, Project administration, Data curation, Writing - review & editing.

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Authors and Affiliations

  1. Faculty of Chemical Engineering, Ho Chi Minh City University of Technology (HCMUT), 268 Ly Thuong Kiet Street, District 10, Ho Chi Minh City, Vietnam

    Nga H. N. Do, Thinh H. Pham, Phung K. Le & Anh C. Ha

  2. Vietnam National University Ho Chi Minh City, Linh Trung Ward, Thu Duc City, Ho Chi Minh City, Vietnam

    Nga H. N. Do, Thinh H. Pham, Phung K. Le & Anh C. Ha

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  1. Nga H. N. Do
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Correspondence to Anh C. Ha.

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Do, N.H.N., Pham, T.H., Le, P.K. et al. Thermo-responsive Chitosan/β-glycerophosphate hydrogels directly post-loading anti-inflammatory diclofenac sodium. J Sol-Gel Sci Technol 105, 451–460 (2023). https://doi.org/10.1007/s10971-022-06020-7

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  • DOI: https://doi.org/10.1007/s10971-022-06020-7

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