title: A novel nanoscale-dispersed eye ointment for the treatment of dry eye disease.
abstract: A novel nanoscale-dispersed eye ointment (NDEO) for the treatment of severe evaporative dry eye has been successfully developed. The excipients used as semisolid lipids were petrolatum and lanolin, as used in conventional eye ointment, which were coupled with medium-chain triglycerides (MCT) as a liquid lipid; both phases were then dispersed in polyvinyl pyrrolidone solution to form a nanodispersion. Single-factor experiments were conducted to optimize the formulations. A transmission electron micrograph showed that the ointment matrix was entrapped in the nanoemulsion of MCT, with a mean particle size of about 100 nm. The optimized formulation of NDEO was stable when stored for six months at 4 °C, and demonstrated no cytotoxicity to human corneal epithelial cells when compared with commercial polymer-based artificial tears (Tears Natural Forte). The therapeutic effects of NDEO were evaluated on a mouse model with 'dry eye'. Both the tear break-up time and fluorescein staining demonstrated therapeutic improvement, displaying a trend of positive correlation with higher concentrations of ointment matrix in the NDEO formulations compared to a marketed product. Histological evaluation demonstrated that the NDEO restored the normal corneal and conjunctival morphology and is safe for ophthalmic application.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Benjamin Tak Kwong
authors.initials: BT
authors.lastname: Lee
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy*; D004655:Emulsions / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D019793:Fluorescein / Q000494:pharmacology; D006801:Humans; D007809:Lanolin / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000009:adverse effects; D009824:Ointments / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions / Q000009:adverse effects* / Q000493:pharmacokinetics*; D010577:Petrolatum / Q000008:administration & dosage; D014280:Triglycerides / Q000008:administration & dosage
chemical_list: D004655:Emulsions; D009824:Ointments; D009883:Ophthalmic Solutions; D014280:Triglycerides; D007809:Lanolin; D010577:Petrolatum; D019793:Fluorescein