Controllable continuous sub-tenon drug delivery of dexamethasone disodium phosphate to ocular posterior segment in rabbit

Figures & data

Figure 1. The picture of sub-tenon embedded tubes in rabbit: (a) the tube sutured on sclera, (b) Sutured on the conjunctive edge, and (c) The tube sutured in the eyelid.

Figure 2. The mean levels of dexamethasone concentrations in the posterior segment tissue at different times in vitreous (a), choroid/retina compound (b), and sclera (c).

Table 1. The dexamethasone concentrations in the posterior segment tissue following CCSDD, IV, SC.

	Vitreum	Choroidal/retinal compound	Sclera
CCSDD group
1 h	71.05 ± 30.23	2522.46 ± 425.94	11192.22 ± 5302.51
3 h	57.23 ± 12.34	3291.35 ± 438.11	9785.20 ± 1964.12
6 h	50.23 ± 13.77	2331.09 ± 454.41	6215.17 ± 1871.83
10 h	50.51 ± 8.40	1796.19 ± 380.36	4053.03 ± 1330.47
11 h	42.84 ± 6.24	1518.52 ± 332.81	3857.47 ± 1508.05
12 h	33.52 ± 5.31	1191.62 ± 303.29	1913.73 ± 389.28
16 h	28.47 ± 4.42	988.97 ± 336.43	1215.48 ± 449.07
20 h	27.78 ± 3.26	812.90 ± 188.26	906.40 ± 312.84
24 h	22.40 ± 4.38	418.20 ± 97.81	484.52 ± 155.25
SC group
1 h	63.19 ± 15.12	1881.83 ± 336.98^a	8604.95 ± 1597.26
2 h	80.45 ± 11.10	3212.63 ± 796.76	6071.65 ± 737.76
3 h	73.77 ± 14.74	3638.80 ± 580.05	4419.68 ± 1006.87^a
4 h	39.65 ± 8.87	1701.27 ± 551.90	2287.56 ± 742.66
6 h	34.53 ± 6.89	1333.65 ± 469.43^a	1645.75 ± 631.69^a
8 h	28.29 ± 4.56	760.86 ± 177.74	1031.78 ± 443.14
12 h	22.68 ± 5.40^a	412.78 ± 88.89^a	463.21 ± 136.14^a
24 h	3.71 ± 4.31^a	184.59 ± 94.86^a	237.94 ± 139.25^a
IV group
1 h	43.78 ± 2.62	140.57 ± 34.56^a	281.42 ± 60.13^a
3 h	30.08 ± 2.55^a	284.82 ± 23.14^a	402.99 ± 96.49^a
6 h	21.53 ± 2.66^a	90.75 ± 12.08^a	141.57 ± 31.46^a
12 h	5.34 ± 5.11^a	38.94 ± 13.00^a	64.38 ± 11.83^a
24 h	1.37 ± 2.14^a	3.71 ± 4.50^a	22.23 ± 7.44^a

CCSDD group: the dexamethasone concentration in rabbit posterior segment at 1, 3, 6, 10, 11, 12, 16, 20 and 24 h after first dose of 0.3 ml (5 mg/ml) DEXP, and then continuous release of DEXP (5 mg/ml) at the rate of 0.1 ml/h for 10 h. SC group: the dexamethasone concentration at 1, 2, 3, 4, 6, 8, 12 and 24 h after subconjunctival injection of 0.3 ml (5 mg/ml) DEXP, IV group: the dexamethasone concentration at 1, 3, 6, 12 and 24 h after intravenous injection of 1 mg/kg DEXP in the rabbits. (Comparing the dexamethasone concentration at 1, 3, 6, 12 and 24 h between the three groups, ^adenotes that compared with CCSDD group, the difference was statistically significant.). The bold values (1h, 3h, 6h, 12h, 24h) is the same time point in three group.

Figure 3. Levels of dexamethasone concentration in vitreous (a), choroid/retina compound (b), sclera (c). (*denotes that compared with CCSDD group, the difference was statistically significant).

Chart 1. The illustration of the time in CCSDD group.

Table 2. The pharmacokinetic parameters of dexamethasone in the rabbits' posterior segment tissue following CCSDD, IV, SC.

	Vitreum	Choroidal/retinal compound	Sclera
CCSDD group
Cmax (ng/ml)	71.05	3219.35	11192.20
Tmax (h)	1	3	1
AUC0–24 (ng*h/ml)	1411.65	41400.70	93577.80
T1/2 (h)	14.32	7.65	4.89
SC group
Cmax (ng/ml)	80.45	3638.80	8604.95
Tmax (h)	2	3	1
AUC0–24 (ng*h/ml)	628.84	22411.70	35582.30
T1/2 (h)	5.51	8.29	6.26
IV group
Cmax (ng/ml)	43.78	284.82	402.99
Tmax (h)	1	3	3
AUC0–24 (ng*h/ml)	285.23	1571.71	2858.71
T1/2 (h)	4.52	3.85	6.88

Cmax: peak concentration; Tmax: time to peak concentration; AUC_0–24: area under the concentration–time curve between 0 and 24 h; T_1/2: elimination half-life.