Flurbiprofen loaded thermosensitive nanohydrogel for ophthalmic anti-inflammatory therapy

Based on the advantages of nanostructured lipid carriers (NLCs) promoting transcorneal penetration and in-situ gel prolonging precorneal retention, this study aimed to develop a thermosensitive NLCs integrated nanohydrogel for enhancing the drug bioavailability of flurbiprofen (FB) after topical ophthalmic administration. FB loaded NLCs (FB-NLCs) and thermosensitive FB-NLCs integrated nanohydrogel (FB-NLCs-Gel) were prepared using the melt-emulsification and cold methods, respectively. The nanohydrogel was optimized by the Central Composite Design method, and the optimum formulation selected was 27.36% and 6.22% (w/v) for P407 and P188 , respectively. The sol–gel transition temperatures of undiluted and diluted by artificial tear fluid (ATF) were 28.5 ± 0.4 °C and 32.8 ± 0.9 °C, respectively. And viscosity tests demonstrated that the prepared nanohydrogel showed the effects of anti-tear fluid dilution. The Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) and cytotoxic tests indicated that the FB-NLCs-Gel formulation was non-irritating. In vivo pharmacokinetic studies showed the AUC (0–6h) of FB-NLCs-Gel was 1.93-fold that of FB-Sol and 1.42-fold that of FB-NLCs, suggesting that FB-NLCs-Gel could significantly enhance the bioavailability of FB in aqueous humor. On topical application against rabbit ocular inflammation, the nanohydrogel exhibited superior therapeutic efficacy over that of the FB solution via inhibiting the level of IL-6, TNF-α and PGE 2 in both aqueous humor and tears. Overall, this work has evidenced that the FB-NLCs integrated nanohydrogel would be a promising candidate for ophthalmic anti-inflammatory therapy.