# Contact Lenses as Drug Delivery System for Glaucoma: A Review
## 3 Contact Lens Drug Delivery in Glaucoma
### Soaking  
The first approach was made with the soak and release method using pilocarpine [69]. After that, some modifications were made to achieve better results [71; 72; 140; 149; 150; 149; 151], reaching the same deduction with 2 h of contact lens loaded with 1% pilocarpine worn, than with 4% pilocarpine drop treatment [71]. The same strategy was also used with other drugs such as timolol and brimonidine, showing equivalent control of IOP using CLs only 30 min per day during 14 days [141]. Furthermore, the use of CLs decreases the possibility of an undesired systemic effect as showing no changes in IOP of untreated eyes [152].  
This method has also been used with new potential treatments for glaucoma, such as melatonin and analogues (Figure 2) showing a prolonged release of the drugs during the first 30 min. In the case of dinucleotides such as Ap4A and Gp4G (Figure 3) there is a more sustained release of the compounds during the first 60 min and lasting for 3 h. Furthermore, it was proven that it could be used during 3 consecutive days with a similar release if CL were soaked overnight with the drug. This fact opens a new possibility for using multipurpose solutions as protectors and carriers of drugs, recharging each night CLs with the selected drug (non-published data).  
Figure 3: Soak and release method used with the dinucleotides Ap4A and Gp4G. There is a substantial release of drugs during the first 60 min, lasting 3 h that could be used for at least 3 consecutive days. This fact opens a new possibility for using multipurpose solutions such as protectors and carriers of drugs, recharging each night the CL with the selected drug. (Balafilcon A. Silicon Hidrogel ionic).  
Figure 2: Soak and release method used with melatonin and analogues. There is a substantial release of drugs during the first 30 min and lasting for 2 h. (Balafilcon A. Silicon Hidrogel ionic).  
It is worth noting that only using contact lenses for 30 min per day, has an equivalent control of IOP than with eye drops [141]. Nevertheless, no study showed a prolonged drug release exceeding 3 h, which implies the need to produce modified CLs with different characteristics to increase the efficacy.  
The addition of vitamin E into the matrix of hydrogels creates a biocompatible diffusion barrier that extends the drug release over time [143]. In this sense, timolol loaded in vitamin E modified lenses showed good IOP control, requiring only 20% of the dose used in drop treatment and lasting four days [49].  
Similar results were obtained by [PERSON] et al. [91] when using timolol, dorzolamide or a combination of both. The addition of vitamin E increases from 1 to 25 h the release for timolol and from 2.5 to 36 for dorzolamide. An equivalent control of IOP (5 mmHgg) was found using six times less concentration than drop treatment and lasting for up to eight days after treatment cessation [91].  
The same approach has also been used with bimatoprost, showing a controlled release at therapeutic doses beyond ten days [88].  
However, this modification also has its limitations. Although silicone hydrogel compounds show benefits in the release of these drugs [49; 91], pHEMA lenses have not shown any improvement in timolol or bromidine, with the addition of vitamin E [153].  
Even within silicone hydrogels, there are studies that do not find benefits in the use of vitamin E compared to lenses without this pre-treatment [151]. The uncertainty caused by the behaviour of the different materials, as well as the negative impact on oxygen diffusion and ion permeability, are the main drawbacks of this technique [143].