Design and evaluation of carnosic acid-loaded thermosensitive lipidic nanogels for nasal delivery: ex vivo permeation, nasal ciliotoxicity, and antioxidant assessment.

Carnosic acid (CA) is a diterpene phenolic compound derived from the leaves of , known for its neuroprotective, anti-inflammatory, and antioxidant properties. However, its effectiveness is limited due to poor solubility and a low dissolution rate. To enhance its neuroprotective potential, a thermosensitive intranasal nanogel incorporated with CA-loaded nanostructured lipid carriers (NLC) was developed using a quality-by-design approach to improve delivery and efficacy of CA. NLC were developed by melt emulsification followed by ultrasonication method by employing solid lipid (Precirol® ATO 5), liquid lipid (Capryol 90), and surfactant (Tween 60). The developed NLC was optimized using a central composite design and exhibited a mean particle size of 114.3 ± 2.62 nm, a polydispersity index of 0.285 ± 0.032, and an entrapment efficiency of 75.25 ± 0.71%. Further, thermosensitive in situ gel was developed and optimized for its gelling strength, gelation temperature, texture profile. The developed gel containing the optimized NLC was assessed for in vitro release and ex vivo permeability using goat nasal mucosa followed by antioxidant study. The nasal ciliotoxicity of developed nanogel was reviewed by histopathological study. The nanogel demonstrated a favorable texture profile and gelling strength, with a gelation temperature of 29.63 ± 0.15 °C. In vitro release studies indicated a sustained release of CA, with 52.96 ± 1.69% released over 12 h, and a 2.76-fold increase in nasal permeation compared to the control gel. Antioxidant assays showed that the optimized CA-NLC gel possessed strong free radical scavenging activity, comparable to that of the standard antioxidant, butylated hydroxyanisole. Finally, developed nanogel exhibited safe profile for intranasal delivery as revealed by histopathological study. All these findings confirm the capability of developed thermosensitive in situ nanogel for intranasal delivery.