title: Self-assembled liquid crystalline nanoparticles as a novel ophthalmic delivery system for dexamethasone: Improving preocular retention and ocular bioavailability.
abstract: The object of this study was to design novel self-assembled liquid crystalline nanoparticles (cubosomes) as an ophthalmic delivery system for dexamethasone (DEX) to improve its preocular retention and ocular bioavailability. DEX cubosome particles were produced by fragmenting a cubic crystalline phase of monoolein and water in the presence of stabilizer Poloxamer 407. Small angle X-ray diffraction (SAXR) profiles revealed its internal structure as Pn3m space group, indicating the diamond cubic phase. In vitro, the apparent permeability coefficient of DEX administered in cubosomes exhibited a 4.5-fold (F1) and 3.5-fold (F2) increase compared to that of Dex-Na phosphate eye drops. Preocular retention studies revealed that the retention of cubosomes was significantly longer than that of solution and carbopol gel, with AUC(0-->180min) of Rh B cubosomes being 2-3-fold higher than that of the other two formulations. In vivo pharmacokinetics in aqueous humor was evaluated by microdialysis, which indicated a 1.8-fold (F1) increase in AUC(0-->240min) of DEX administered in cubosomes relative to that of Dex-Na phosphate eye drops, with about an 8-fold increase compared to that of DEX suspension. Corneal cross-sections after incubation with DEX cubosomes demonstrated an unaffected corneal structure and tissue integrity, which indicated the good biocompatibility of DEX cubosomes. In conclusion, self-assembled liquid crystalline nanoparticles might represent a promising vehicle for effective ocular drug delivery.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gan
authors.forename: Shun
authors.initials: S
authors.lastname: Han
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Shen
authors.forename: Jiabi
authors.initials: J
authors.lastname: Zhu
authors.forename: Chunliu
authors.initials: C
authors.lastname: Zhu
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gan
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003315:Cornea / Q000378:metabolism; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D005123:Eye / Q000378:metabolism*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005989:Glycerides / Q000737:chemistry*; D050866:Liquid Crystals; D008297:Male; D017551:Microdialysis; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D036103:Nanotechnology; D009883:Ophthalmic Solutions; D010316:Particle Size; D010539:Permeability; D020442:Poloxamer / Q000737:chemistry; D011817:Rabbits; D053838:Scattering, Small Angle; D013678:Technology, Pharmaceutical / Q000379:methods; D014783:Viscosity; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D005079:Excipients; D005938:Glucocorticoids; D005989:Glycerides; D009883:Ophthalmic Solutions; D014867:Water; D020442:Poloxamer; D003907:Dexamethasone; C005953:monoolein