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Blazaki Styliani, Konstantinos Pachis, Irini Naoumidi, Manolis Tzatzarakis, Miltiadis K Tsilimbaris, Sofia Antimisiaris; Extended release of intravitreal flurbiprofen from a novel thermosensitive hydrogel. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1972.
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© ARVO (1962-2015); The Authors (2016-present)
Thermogelling polymers can be optimized as drug delivery vehicles to enhance drug availability in the vitreous cavity. NSAIDs are rarely used intraocularly due to their short half-life and the necessity of multiple injections. Development of such extended release systems has proven challenging in order to include NSAIDs in treating conditions related with macular edema. In this study, we demonstrate the bioavailability of flurbiprofen embodied in in-situ forming hydrogel in rabbit eyes.
We developed a thermosensitive hydrogel system using Pluronic F-127. Two formulations were used in in vitro release studies to access the bioavailability of flurbiprofen in specific time points: one using polymer alone with flurbiprofen (FT) and another using polymer combined with flurbiprofen loaded liposomes (FTL). The concentration of the drug was 10mg/ml. For in vivo pharmacokinetics, Pigmented rabbits were divided into three groups: those who received intravitreal FT, FTL and flurbiprofen (F) alone. Flurbiprofen concentrations were determined in the vitreous in specific time points (n=3 eyes per time point) with means of HLPC/MS method. Slit lamp examination and indirect fundoscopy were performed prior to any injection and at each time point.
In vitro studies showed a statistical significant difference in all time points between FT and FTL(p-value<0.05). The release from FT and FTL reached a plateau in 48 and 96 hours, respectively. The critical hydrogel is injected through 27G needle as solution which gelates a few seconds post-insertion in the vitreous body. Ophthalmic examinations revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Cmax was estimated F=513,91±76,94, FTL=408,23±4,76, FT=458,05±64,77. AUC was estimated F=1,686,20, FT=1549,74, FTL=1930,78. Higher flurbiprofen concentrations in the first three hours were estimated in both FT and FTL formulations than free drug.
We managed to extend the presence of the drug into the vitreous cavity in short time points. There is a need for greater prolongation of the drug in the vitreous cavity and further experimentation with the system’s structure is currently ongoing.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Polymeric system depicted in scanning electron microscope
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