Dual-action depot formulation of hyaluronic acid/poloxamer in-situ gel enclosing lavender oil-based syringic acid nanoemulsion for enhanced intra-articular treatment of osteoarthritis.

AIM: Osteoarthritis (OA) is a degenerative disorder affecting the joints and is portrayed by chronic pain and inflammation, impacting quality of life. Conventional treatments show limited efficacy due to inadequate drug delivery and suboptimal retention. The unique anti-inflammatory effects of syringic acid (SA) can be potentiated with the incorporation of lavender oil in a nanoemulsion for intra-articular delivery.

METHODS: Integrating a novel hyaluronic acid/poloxamer 407/poloxamer 188 (HA/P407/P188) in situ gel with SA-loaded lavender oil-based nanoemulsion was attempted. Colloidal features and suitability of the corresponding in situ gel for intra-articular delivery were demonstrated. In-vivo therapeutic efficacy on knee osteoarthritis induction model was also investigated.

RESULTS: The proposed nanoemulsion was designed with a droplet size of 214.5 ± 19.54 nm and a polydispersity index of 0.387 ± 0.060. HA/P407/P188 in situ gel further augments therapeutic outcomes for intra-articular administration by prolonging SA release approaching 6 days and offering appropriate sol-gel transition temperature and rheological patterns. In-vivo anti-arthritic activity was confirmed with a more reduced joint inflammation and downregulation of pro-inflammatory cytokine levels in knee joints compared to SA suspension.

CONCLUSIONS: This study highlights the potential of the nanoemulsion in a HA/P407/P188 in-situ gel as a promising strategy for intra-articular OA therapy, with an enhanced sustained therapeutic efficacy.