Controllable release of pirfenidone by polyvinyl alcohol film embedded soft contact lenses in vitro and in vivo.

To increase the amount of pirfenidone (PFD) loaded in polyvinyl alcohol (PVA) film embedded soft contact lens (SCL), and evaluate its function of sustaining delivery of drug in vitro and in vivo. Drug loading efficiency within PVA film and SCLs, drug release from SCLs in vitro, and the effects of parameters of SCLs and external environment on drug release in vitro were evaluated by ultraviolet-visible spectrophotometer at 312 nm. Safety of SCLs was evaluated in vitro by transformed human corneal epithelial cell. Safety in vivo was determined by optical coherence tomography and histology of anterior segment of rabbits. Drug release study in tear fluid and aqueous humor were measured by ultra-performance liquid chromatography. SCLs had smooth surface and were fit for experimental rabbits. Amount of PFD in PVA film and SCLs were 153.515 µg ± 12.508 and 127.438 µg ± 19.674, respectively, PFD in PVA film was significantly higher than SCLs (p=.006) and closed to 150 µg (targeting amount of PFD to be loaded). Thickness of SCLs, molecular weight of PVA, and amount of PVA used in SCLs affected drug release in vitro significantly. Thickness of PVA film and amount of drug in SCLs had no effect on drug release rate in vitro. SCLs were safe in vitro and in vivo, PFD released from SCLs could be detected around 12 hours in tears and aqueous humor, and the concentration of drug was higher than eye drop at all detected time points while amount of PFD in SCLs was lower than eye drop. Drug loaded PVA film embedded SCLs may be a promising ocular drug delivery system.

Extended Delivery of Pirfenidone with Novel, Soft Contact Lenses In Vitro and In Vivo.

Purpose: The aim of this study was to fabricate pirfenidone (PFD)-loaded soft contact lenses (SCLs), explore their characteristics, and evaluate their efficiency on extended delivery of PFD in vitro and in vivo. Methods: PFD-loaded SCLs were fabricated by embedding an insert of PFD and polyvinyl alcohol (PVA) into 2 layers of silicone elastomer. The optical transparency, water content, and protein deposition were measured. Transformed human corneal epithelial cells were used to test the cytotoxicity of SCLs. The release rate of PFD by SCLs in vitro was evaluated by an ultraviolet-visible spectrophotometer. Toxicity of SCLs was assessed by inspection of ocular surface irritation in rabbits before and after contact lens wear. The concentrations of PFD in tears and aqueous humor of rabbits' eyes as a function of time were determined by high-performance liquid chromatography for SCLs and 30 µL of 0.5% PFD eye drops. Results: SCLs possessed good light transmittance. Blank SCLs had poor water content (0.548% ± 0.330), and an improved water content was found in PVA film-loaded SCLs (11.022% ± 1.508, P = 0.010). No lysozyme and human serum albumin were found in SCLs. There was no significant toxicity of SCLs in vitro and in vivo. SCLs prolonged the residence time of PFD in tears and aqueous humor of rabbit eyes by 5 times compared with the eye drop instillation while around 1/10 of the eye drop dosage was loaded in SCLs. Conclusions: PFD-loaded SCLs can significantly prolong the residence time of PFD and may be a promising ocular drug delivery system.