Table 1.
Pharmacokinetic analysis of the penetration of IMC-NPs in rabbit corneas treated at cold temperature (4°C) or with endocytosis inhibitors
| Jc (nmol/cm2/h) | Kp 10-4 (× /h) | Km (×10-2) | τ (h) | D (×10-4 cm2/h) | |
|---|---|---|---|---|---|
|
| |||||
| Normal (37°C treatment) | 150.6±16.2 | 109.8±9.7 | 50.8±5.3 | 0.51±0.03 | 123.2±11.8 |
| 4°C treatment | 35.3±3.1*,# | 28.1±2.2*,# | 10.5±1.6*,# | 0.92±0.10*,# | 98.7±9.5*,# |
| Vehicle | 158.4±14.7 | 113.3±10.7 | 52.4±4.8 | 0.48±0.04 | 135.2±13.1 |
| Nystatin | 88.8±8.2*,# | 63.5±6.8*,# | 35.0±3.9*,# | 0.57±0.06 | 113.5±12.7 |
| Dynasore | 111.3±9.9*,# | 85.3±7.3*,# | 47.0±4.3 | 0.52±0.05 | 125.4±11.9 |
| Rottlerin | 111.6±9.9*,# | 85.6±7.1*,# | 56.8±5.3 | 0.54±0.07 | 147.7±9.1 |
| Cytochalasin D | 131.6±12.6 | 94.2±9.0 | 50.4±2.9 | 0.54±0.03 | 143.7±16.3 |
| Nys + Dyn + Rot | 40.1±4.1*,# | 36.3±3.2*,# | 15.9±1.5*,# | 0.89±0.09*,# | 99.5±9.9*,# |
Notes: Parameters were calculated according to Equations 1–3 (see Materials and methods). The experiments were performed at normal (37°C) and cold (4°C) temperatures. In the study using endocytosis inhibitors, the corneal samples were co-treated with IMC-NPs and inhibitors (0.5% DMSO [vehicle], 54 µM nystatin, 40 µM dynasore, 2 µM rottlerin or 10 µM cytochalasin D). Nys + Dyn + Rot indicates the multi-treated groups, which were treated with 54 µM nystatin, 40 µM dynasore and 2 µM rottlerin. n=5–8.
P<0.05, vs Normal for each category.
P<0.05, vs Vehicle for each category.
Abbreviations: D, diffusion constant within the cornea; IMC-NPs, ophthalmic formulation containing indomethacin nanoparticles; Jc, indomethacin penetration rate; Km, cornea/preparation partition coefficient; Kp, penetration coefficient through the cornea; τ, lag time.