Design and Optimization of Self-Nanoemulsifying Drug Delivery Systems to Enhance the Anti-Inflammatory Efficacy of Derris scandens (Roxb.) Benth. Extract.

Background/Objectives:Derris scandens (Roxb.) Benth. stem extract (DSE) is used in Thailand for musculoskeletal pain, but its bioactive, lupalbigenin, has limited aqueous solubility. This study aimed to develop a DSE-loaded self-nanoemulsifying drug delivery system (DSE-SNEDDS), characterized its nanoemulsions, and compared their anti-inflammatory activity and stability. Methods: Various extraction methods were compared to obtain a high yield of lupalbigenin. A D-optimal design was used to optimize SNEDDS composition based on the apparent solubility of lupalbigenin. The selected preconcentrate was diluted fivefold to prepare DSE nanoemulsion (DSE-NE). Droplet characteristics, RAW 264.7 cell viability, LPS-induced nitric oxide production, and 12-week stability at 4, 25, and 40 °C were assessed. Results: Ultrasound-assisted extraction gave the highest lupalbigenin content (108.69 ± 0.12 µg/mg DSE). The selected formulation contained 20% Lexol® GT-865, 40% Kolliphor RH40, 30% Transcutol, and 10% ethanol. Fivefold dilution produced DSE-NE with a droplet size of 172.5 ± 0.3 nm and polydispersity index of 0.31 ± 0.01. Its IC50 was 4735 µg/mL formulation (94.70 µg/mL DSE equivalent), compared with 31.57 µg/mL for DSE in DMSO. At 40 µg/mL DSE equivalent, DSE-NE and DSE in DMSO inhibited nitric oxide production by 78.79 ± 2.31% and 50.78 ± 2.95%, respectively; matched blank NE produced 36.53 ± 6.45% inhibition. During storage, the preconcentrate retained 95-96% of lupalbigenin and generated nanoemulsions with minimal size changes, whereas preformed DSE-NE retained 81-87% and showed greater droplet growth. Conclusions: These results support the selection of the preconcentrate as the preferred storage form for further topical formulation development. However, skin delivery, dermal safety, and topical efficacy remain to be established.