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

• Published in: Journal of sol-gel science and technology 2023-02, Vol.105 (2), p.451-460
• Main Authors: Do, Nga H. N., Pham, Thinh H., Le, Phung K., Ha, Anh C.
• Format: Article
• Language: English
• Subjects: Ceramics; Chemistry and Materials Science; Chitosan; Composites; Diclofenac; Dissolution; Genipin; Glass; Glycerophosphate; Hydrogels; Inorganic Chemistry; Materials Science; Nanotechnology; Natural Materials; Nonsteroidal anti-inflammatory drugs; Optical and Electronic Materials; Original Paper: Sol-gel and hybrid materials for biological and health (medical) applications; Physiological effects; Pore size; Sodium; Sol-gel processes; Solvents; Swelling ratio
• ISSN: 0928-0707; 1573-4846
• DOI: 10.1007/s10971-022-06020-7

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 m 2 /g, 4.16–4.61 nm, and 0.08–0.28 cm 3 /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.