Thermo-responsive in situ gel of fluticasone propionate nanosuspension modified with carboxymethyl chitosan for enhanced blepharitis therapy.

Blepharitis (BLE) is a common eyelid inflammation with irritation and discomfort, which can lead to meibomian gland dysfunction and dry eye. However, most of the conventional eye drops for BLE have insufficient retention and poor solubility in the eyes, resulting in sub-optimal therapeutic effect. Herein, we prepared fluticasone propionate (FP) nanosuspensions (FP-NSs) modified by carboxymethyl chitosan, then a thermo-responsive in situ gel we constructed by encapsulating FP - NSs within the hydrogels matrix (SEP) synthesized from selenide (Se), Polyethylene glycol (PEG) and polypropylene glycol (PPG). Specifically, the FP nanosuspensions can improve their solubility and stability due to small particle size (274.6 ± 1.60 nm), the minimum PDI (0.267 ± 0.03) and large absolute zeta-potential value (38.17 ± 0.7 mV). FP nanosuspension-loaded thermo-responsive in situ gel (NS-SEP- G) exhibits. Temperature-sensitive sol-gel transition behavior (37 °C), a long-lasting drug release and ocular retention time via the hydrophobic interaction. In a BLE rat model, NS-SEP-G produces notable therapeutic benefits such as increasing tear secretion, reducing eyelid swelling and conjunctival capillary dilatation, inhibiting inflammatory substance infiltration and expression of inflammatory factors. Meanwhile, NS-SEP-G shows good biocompatibility in in-vitro cytotoxicity tests and eye irritation in mice. Based on this study, this paper provides a more convenient and effective drug option for the treatment of BLE.