Transscleral Delivery of Nanoparticle Triamcinolone

Abstract

 

Purpose:

 

To determine the ex vivo and in vivo transscleral permeability of nanoparticle triamcinolone (NTA) compared with commercially available triamcinolone acetonide (TA).

 

Methods:

 

The ex vivo permeability of NTA and TA (1.5 mg/ml) across human donor sclera was tested using a Lucite block perfusion chamber. Levels of NTA diffusing across the sclera were measured every 2 hours for 24 hours using HPLC. Pigmented rabbits (2.2 Kg) were given a subtenon injection in vivo in both eyes with NTA (1.0 mg/ 0.2 ml) or TA (20 mg/0.2 ml). One group (n = 20) of rabbits were euthanized at 2, 4, 6 hours post injection, enucleated, frozen, and dissected into different tissues. The second group of rabbits (n = 20) were euthanized at 2, 4, 6 hours post injection, enucleated, frozen, desiccated, and dissected into different tissues. Each group had a control (n = 4) and immediate euthanasia subgroups (IE) (n = 4) which were enucleated at 6 hours post injection. Drug concentration in the dissected tissues was measured using HPLC.

 

Results:

 

Ex vivo NTA had a faster transscleral permeability constant (K_const) of 1.09 ± 0.42 x 10^-5 cm/s compared to TA at 5.93 ± 2.90 x 10^-9 cm/s. After 6 hours, retina/choroid level of TA was 3.78 ± 2.31 ng/mg and 1.91 ± 0.59 ng/mg with NTA. Vitreous level was 0.24 ± 0.22 ng/ml with TA and 9.73 ± 5.14 ng/ml with NTA after 6 hours. In dessicated eyes, TA concentration in the retina was 1.94 ± 0.65 ng/ml without immediate euthanasia (IE) and 34.89 ± 6.68 ng/mg with IE. TA concentration in the choroid was 12.71 ± 5.59 ng/mg without IE and 26.98 ± 4.44 ng/mg with IE at 6 hours.

 

Conclusions:

 

Both TA and NTA are able to diffuse across human and rabbit sclera. The retina/choroid concentration is comparable in both TA and NTA, however, NTA showed higher vitreous concentration with a small dose. Based on the dry desiccated tissue data, the choroid is a major barrier in transscleral drug delivery of TA and NTA.  

 

Keywords: drug toxicity/drug effects • retina • vitreous