Mucoadhesive bilayer nanomicelles-in-nanofibers nasal insert for sustained treatment of dry eye disease.

Dry eye disease (DED) is a common medical condition that affects quality of life and limits work productivity. Conventional eye drops remain the most common treatment but are limited by low bioavailability and the need for frequent application to sustain therapeutic effect. The current study involves the development of innovative non-invasive single-dose mucoadhesive varenicline (VAR)-loaded biodegradable and biocompatible nanomicelles-in-nanofibers (NFs) nasal insert for DED treatment. The insert has a bilayer structure: the first layer is coaxial NFs and is composed of free VAR-loaded polyethylene oxide (PEO) core and a shell of 1:9 (w/w) polycaprolactone (PCL) and cellulose acetate (CA). Hydrophilic CA was incorporated into the hydrophobic PCL shell to act as exit channels allowing sustained VAR release from the NFs core towards prolonged therapeutic activity. The second layer is to improve mucoadhesiveness and stimulate fast-term drug release to impede inflammation promptly. This second layer is made of electrospun chitosan (CS)/PEO NFs incorporating both VAR-loaded pluronic-F127 nanomicelles (VAR-NPs) and free VAR. The fabricated VAR-NPs and VAR-NPs-in-NFs nasal inserts were characterized using DLS, FTIR, tensile strength, porosity, hydrophilicity, swelling, degradation %, SEM, TEM, and fluorescent micrographs. VAR loading capacity and entrapment efficiency in VAR-NPs were 23.7 and 95 %, respectively. In-vitro VAR release from VAR-NPs and nasal insert was determined after 8 and 16 days, respectively. Cell viability % investigation of human oral epithelial cells (OECs) proves the safety of the developed formulations. In-vivo evaluation including analysis of histological micrographs of the corneal structure, revealed clear signs of structure improvement. The newly developed VAR-NPs-in-NFs nasal inserts can serve as an effective alternative to conventional eye drops for treating DED and offer a progressive strategy with considerable potential for broader application across various ocular diseases beyond DED.