Poloxamer 407/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery

• DOI: 10.1021/acs.molpharmaceut.7b00939
• Publication Date: 2018-01-09T20:42:15Z
• Authors: Maria A. Grimaudo; Silvia Pescina; Cristina Padula; Patrizia Santi; Angel Concheiro; Carmen Alvarez-Lo...; Sara Nicoli
• Keywords: Poloxamer 407; Zeta potential

Cyclosporine is an immunosuppressant agent approved for the treatment of dry eye disease and used off-label other ocular pathologies. Its formulation bioavailability present a real challenge due to large molecular weight (1.2 kDa), high lipophilicity, low water solubility. The aim work was develop aqueous micellar efficient cyclosporine delivery tissues, using water-soluble derivative vitamin E (TPGS: d-α-tocopheryl polyethylene glycol 1000 succinate) poloxamer 407 (Pluronic ®F127) as excipients. mixed micelles were characterized in terms particle size, zeta potential, rheology, stability upon dilution freeze-drying. Additionally, enzymatic-triggered release succinate from TPGS investigated vitro presence esterase. Compared commercially available ophthalmic formulation, 407:TPGS 1:1 molar ratio significantly improved solubility, which increased proportionally surfactant concentration reaching 0.4% (w/v) 20 mM total concentration. Cyclosporine-loaded efficiently retained drug once diluted simulated lachrymal fluid and, concentration, stable drug-loaded applied ex vivo on porcine cornea compared Ikervis®. Drug accumulation resulted proportional (6.4 ± 1.9, 17.6 5.4, 26.9 7.4 μgdrug/gcornea, after 3 h 1, 2.5, 4 mg/mL respectively). containing (20 surfactant) also evaluated sclera, with view targeting posterior segment. results demonstrated capability diffuse into sclera sustain (28 7, 38 10, 57 9, 145 27 μg/cm2 accumulated 3, 6, 24, 48 Reservoir effect experiments that can be slowly released underlying tissues. Finally, all formulations developed this successfully passed HET-CAM assay evaluation irritability.