Reducing allergic reaction and enhancing anti-inflammatory effect of dehydroandrographolide through dehydroandrographolide prodrug liposomes

Andrographolide (AND) and 14-deoxy-11, 12-dide-Hydroandrographolide (dehydroandrographolide, 14-DDA) are widely utilized traditional Chinese medicines for the treatment of inflammation. However, allergic reactions continue to be a concern. This research aimed to reduce allergic reactions and enhance the anti-inflammatory properties of 14-DDA by means of a liposome delivery system. To overcome the low encapsulation efficiency of conventional 14-DDA liposomes, a new 14-DDA derivative, dehydroandrographolide-divaline ester hydrochloride (DADH), was created by introducing valine groups at the C-3 and C-19 positions. DADH liposomes (DADH-lip) achieved high encapsulation efficiency (over 90%) via an ethanol injection method - pH gradient method. The lowest IC 50 value (16.34 μg/mL) of DADH-lip against P815 cells indicated that DADH-lip significantly reduced allergic reactions. In addition, DADH solution (DADH-sol) and DADH liposome decreased the amount of histamine released at both the high (1 mg/mL) and low (20 μg/mL) concentration dosages compared to the commercially available preparation. DADH-lip and DADH-sol also had significant effects in the LPS-induced RAW 264.7 macrophage model. In vivo anti-inflammatory results demonstrated that, compared to commercially available preparations, DADH-lip has a superior therapeutic effect and significantly reduces rat paw swelling. Collectively, DADH-lip with high encapsulation efficiency reduced allergic reactions significantly and enhanced therapeutic effect, suggesting that it may be a promising platform for inflammatory therapy.