# In Vivo Efficacy of Contact Lens Drug-Delivery Systems in Glaucoma Management. A Systematic Review
## 3 Results
### Vitamin-E-Loaded CL  
To extend the drug release time and prolong the therapeutic effect, a physical barrier may be added to the CL matrix, without altering CL transparency and oxygen permeation [53]. To pursue this solution, the CL can be soaked in a vitamin E ethanol before soaking in the drug solution or a vitamin E ethanol can be added to the drug solution, followed by ethanol removal with water (Figure 3) [53].  
[PERSON] and colleagues tested a vitamin-E loaded-CL in dogs affected by primary OAG [37,38]. In a first study, a vitamin-E-loaded CL was compared to a CL without  
Figure 3: Vitamin E effect on drug diffusion through the polymeric matrix of a CL. Reproduced with permission from [53], @Copyright 2015, Elsevier.  
barrier and to timolol eyedrops. Both CL types were soaked in two timolol solution, one at 2.65 mg/mL and one at 8 mg/mL, to allow a drug release capacity of 67 ug and 200 ug, respectively. The drug release capacity of 0.5% timolol eyedrop was estimated at 150 ug. Five treatment groups were designed, and the contralateral eyes constituted the control group. IOP-lowering was not statistically different among treated groups; however, eyedrops treatment showed a significantly higher bilateral IOP reduction than CL groups. This effect seemed related to the increased systemic uptake, supporting that the CL drug-delivery system reduced it. Also, no statistical difference in IOP-lowering was reported between the CL with vitamin E or without. However, in this study, the CL was replaced every day. Nevertheless, in 24 h, the vitamin E CL released only 80% of their drug capacity. Finally, dogs with the vitamin-E-loaded CL did not report any systemic or local toxicity [37].  
In the following study with identical CL applied on glaucomatous dogs, [PERSON] et al. replaced the CL without barrier every 24 h or every four days, and the vitamin-E-loaded CL every four days [38]. The vitamin E CL showed similar efficacy to eyedrops and the CL without barrier replaced daily, without signs of toxicity or hypoxia. Conversely, the CL without barrier replaced every four days failed to lower the IOP significantly [38].  
The vitamin-E-loaded CL was also soaked with two drugs (e.g., timolol and dorzzolamide) [39]. In particular, the CL without barrier and the vitamin E CL were able to release 217.8 ug and 676.7 ug of dorzolamide and 60.6 ug and 191.4 ug of timolol, respectively. The co-loading extended drug delivery time compared to the single-drug-loaded lens. This effect could be related to hydrogen bonding between drug molecules. The vitamin E co-loaded CL was able to extend drug delivery up to 48 h in vitro. Moreover, the IOP-lowering continued for a week after CL removal maybe thanks to drug accumulation inside corneal epithelial cells in beagle dogs. It opened the possibility of wearing a CL for a day to obtain a therapeutic effect lasting a week. The vitamin E CL also achieved a superior IOP-lowering to that of eyedrops (4.35 \(\pm\) 0.18 mmHg versus 3.79 \(\pm\) 0.28 mmHg), with an 11-fold lower drug dose. No ocular or systemic toxicity was reported [39].  
Vitamin A has recently been used as a physical barrier to extend drug delivery time, although only in vitro study was available [54].