In vivo studies of precorneal retention of sodium fluorescein

Topical administration of ocular drops often results in poor drug bioavailability because of poor permeability of the cornea, tear reflex, nasolacrimal drainage, blinking and non-corneal absorption [1]. In situ gelling systems that convert from a liquid formulation to a gel upon ocular administration can offer an improved precorneal retention, which results in enhanced drug bioavailability. Triblock copolymers of polyethylene glycol-b-polypropylene glycol-b- polyethyleneglycol available commercially as Pluronics® are known to exhibit ability of forming gels in situ in response to increase in environmental temperature.Here we have evaluated the retention of sodium fluorescein on corneal surfaces, mediated with Pluronic F127 and Pluronic F68, both in vitro and in vivo.

In vitro experiments were performed using freshly excised cornea from bovine eyes received from P.C. Turner Abattoir (Hampshire, UK). In vivo experiments were conducted using chinchilla rabbits (2.5-3.0 kg). During the experiments rabbits were placed in restraining boxes, where their eye and eye-lid movements were not restricted. 70 pL of 1 mg/mL fluorescein sodium solutions in 20 w/v % Pluronic F-127 and Pluronic F-68 were administered on rabbits’ right eye cornea in the beginning of each experiment. Maximal retention of sodium fluorescein on the cornea was observed for the formulation containing 20 w/v % Pluronic F127, which is related to its gelation in situ at ocular temperature (35-37 °C). The other formulations containing Pluronic F68 and Pluronic F127-Pluronic F68 50:50 % mixtures did not form gels at this temperature and exhibited weaker retention on the cornea. The least retaining formulation was the solution of sodium fluorescein in deionised water. Good correlation was observed for the retention of sodium fluorescein on bovine cornea in vitro with the in vivo results in rabbits. The solution of sodium fluorescein containing 20 w/v % Pluronic F127 formed a gel upon ocular administration and exhibited an improved retention compared to the dye formulation containing 20 w/v % Pluronic F68 as a non-gelling system. The analysis of tear fluid taken from rabbits’ eye indicated a relatively quick decline in sodium fluorescein concentration for all formulations used. However, this decline was much slower when Pluronic F127 was used. The precorneal concentration of sodium fluorescein was 0.514±0.405 pg/mgtear fluid immediately after the ocular administration of Pluronic F127 formulation and it declined to 0.074±0.064 pg/mgtear fluid after 30 mins. Pluronic F127 exhibited in situ gelling properties in vivo and facilitated retention of sodium fluorescein on the corneal surface for up to 15-20 mins. Solutions of Pluronic F68 did not form gels in vivo and they did not provide a substantial improvement in the retention of sodium fluorescein. In vitro experiments performed using freshly excised bovine cornea showed a good correlation with in vivo retention of sodium fluorescein in rabbits.

 

References

  1. 1. Morrison, P.W.J.; Khutoryanskiy, V.V. Ther. Deliv. 5, 1307-1325(2014)
  2. 2. Cho, K.Y.; Chung, T.W.; Kim, B.C.; Kim, M.K.; Lee, J.H.; Wee, W.R.; Cho, C.S. Int. J. Pharm. 260, 83-91 (2003)
Year: 2018
City: Shymkent
Category: Medicine