Thermoreversible gel for delivery of activin receptor-like kinase 5 inhibitor SB-505124 for glaucoma filtration surgery.
The purpose of this study is to investigate a thermoreversible gel using Pluronic F-127 to deliver an activin receptor-like kinase 5 (ALK-5) inhibitor SB-505124 in glaucoma filtration surgery (GFS). The gel was characterized for in vitro drug release and viscosity studies. Cytotoxicity of Pluronic F-127 was examined by MTT assay using cultured rabbit subconjunctival fibroblasts. In addition, Pluronic F-127 gel (18% w/v) containing 5 mg of SB-505124 was applied at the surgical site in an in vivo rabbit GFS model. In the in vitro viscosity study, the gel showed a change in viscosity (from 1000 cps to 45,000 cps) from low temperature (10°C) to body temperature (37°C). The in vitro drug release study demonstrated 100% drug release within 12 h. The gel did not show cytotoxicity to the cultured rabbit subconjunctival cells by MTT assay. In the in vivo rabbit GFS model, the drug was successfully delivered by injection and no severe post-surgical complications were observed. A thermoreversible gel system with SB-505124 was successfully prepared and delivered for the rabbit GFS model, and it may provide a novel delivery system in GFS.
Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA. vsutariya@neomed.edu
Vijaykumar
V
Sutariya
Nicholas
N
Miladore
Werner
W
Geldenhuys
Deepak
D
Bhatia
Daniel
D
Wehrung
Hiroshi
H
Nakamura
D000818:Animals; D052117:Benzodioxoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D001831:Body Temperature; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D018463:Filtering Surgery / Q000379:methods*; D005782:Gels; D005901:Glaucoma / Q000601:surgery*; D007093:Imidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D020442:Poloxamer / Q000737:chemistry / Q000633:toxicity; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D011817:Rabbits; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D013696:Temperature; D013997:Time Factors; D014783:Viscosity
C519132:2-(5-benzo(1,3)dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride; D052117:Benzodioxoles; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D007093:Imidazoles; D011725:Pyridines; D018125:Receptors, Transforming Growth Factor beta; D020442:Poloxamer; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I