Polymeric Azelaic Acid-loaded Nanocapsules Incorporated into Tragacanth Gum: Development and Biological Evaluation in Alternative Models for the Treatment of Rosacea.

Rosacea is an inflammatory skin disorder that significantly impairs patients' quality of life. Azelaic acid (AZA), a well-established keratolytic and anti-inflammatory agent; however, its clinical application is often limited by local adverse effects that reduce patient adherence. In this context, nanotechnology-based drug delivery systems, particularly polymeric nanocapsules, represent a promising strategy to improve physicochemical stability, reduce cutaneous irritation, and enable incorporation into semi-solid formulations with enhanced skin interaction. This study aimed to develop and characterize AZA-loaded polymeric nanocapsules incorporated into tragacanth gum-based hydrogels as a safe, effective, and patient-friendly therapeutic alternative for rosacea. The nanocapsules exhibited a uniform nanometric size (185.66 ± 2.08 nm), low polydispersity index (0.12 ± 0.02), slightly negative zeta potential (- 8.67 ± 0.26 mV), and a skin-compatible acidic pH (3.56 ± 0.16). Drug loading reached 0.53 mg/mL, with an encapsulation efficiency of 42.20%. In vitro cytocompatibility assays showed cell viability close to 100% after 12 and 24 h of exposure, confirming the safety of the system. Antiangiogenic assays using chicken embryos further supported its biocompatibility. The hydrogels displayed a slightly acidic pH and pseudoplastic flow behavior described by the Herschel-Bulkley model, along with higher adhesiveness than liquid suspensions, favoring topical application. Both conventional AZA hydrogels (TG-AZA) and nanocapsule-based hydrogels (TG-NC-AZA) promoted effective drug retention within the stratum corneum. Notably, TG-NC-AZA showed a non-irritant profile in HET-CAM and CAM-TBS assays and demonstrated pronounced anti-inflammatory activity, achieving a 75% reduction. Overall, these findings highlight TG-NC-AZA as an innovative and clinically relevant therapeutic approach for rosacea.