Self-assembled liquid crystalline nanoparticles as a novel ophthalmic delivery system for dexamethasone: Improving preocular retention and ocular bioavailability

• Published in: International journal of pharmaceutics Vol. 396; no. 1; pp. 179 - 187
• Main Authors: Gan, Li, Han, Shun, Shen, Jinqiu, Zhu, Jiabi, Zhu, Chunliu, Zhang, Xinxin, Gan, Yong
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30.08.2010; Elsevier
• Subjects: Administration, Topical; Animals; Aqueous Humor - metabolism; Biological and medical sciences; Biological Availability; Chemistry, Pharmaceutical; Cornea - metabolism; Cryoelectron Microscopy; Crystallography, X-Ray; Cubosome; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - chemistry; Dexamethasone - pharmacokinetics; Drug Carriers; Drug Compounding; Excipients - chemistry; Eye - metabolism; General pharmacology; Glucocorticoids - administration & dosage; Glucocorticoids - chemistry; Glucocorticoids - pharmacokinetics; Glycerides - chemistry; Liquid Crystals; Male; Medical sciences; Microdialysis; Microscopy, Electron, Transmission; Nanoparticles; Nanotechnology; Ocular bioavailability; Ophthalmic delivery; Ophthalmic Solutions; Particle Size; Permeability; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poloxamer - chemistry; Preocular retention; Rabbits; Scattering, Small Angle; Technology, Pharmaceutical - methods; Viscosity; Water - chemistry; Preocular retention; Dexamethasone; Ophthalmic delivery; Ocular bioavailability; Cubosome; Delivery system; Corticosteroid; Pharmaceutical technology; Steroid hormone; Nanoparticle; Antiinflammatory agent; Bioavailability; Retention; Eye; Ophthalmic preparation; Microparticle; Pharmacokinetics
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2010.06.015

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 Pn3 m 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→180 min 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→240 min 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.