# Contact Lenses as Drug Delivery System for Glaucoma: A Review
## 2 Drug Delivery Systems with Contact Lenses  
Contact lenses are divided into two main groups according to their material: soft contact lenses, which are composed of hydrogel or silicone-hydrogel polymers, or rigid gas permeable (RGP) contact lenses. Soft materials are of more interest to be used as drug delivery systems due to their hydrophilic properties, biocompatibility, and comfort [63; 64]. Furthermore, soft contact lenses represent 87% of fits in clinical practice, as opposed to 13% of RGP contact lenses [65; 66]. 2-Hydroxy methyl methacrylate (HEMA) is the most common monomer used to manufacture soft contact lenses, together with N-Vinylpyrrolidone (NVP) in second place, among others. These monomers show suitable properties to be safely used over the ocular surface, such as oxygen permeability, water content, and wettability [63; 64]. Also, their mechanical properties allow soft contact lenses to fit well to the shape of the eye [67]. Other monomers can be incorporated into the matrix of contact lenses to improve these mentioned properties. Based on the water content and ionicity of hydrogels, the Food and Drug Administration (FDA) classifies soft contact lens materials into five groups, which are summarized in Table 2. Hydrogel materials are in groups I, II, III, and IV, while silicone-hydrogels are in group V.  
In 1965, [PERSON] [68] used soft contact lenses as drug delivery systems for the first time. These contact lenses were soaked in a solution containing 1% homatropine, which increased the pupil size of participants compared to a single topical instillation of the solution. In the following decade, different studies imitated this technique to enhance the effect of pilocarpine for acute glaucoma treatment [69; 70; 71; 72]. By soaking soft contact lenses in drug solutions, their residence time over the ocular surface depends on the exchange between these solutions and tears. In this sense, [PERSON] et al. [73] determined that tear exchange while wearing soft contact lenses was around 30 min, compared to 5 min with no lens. Because the molecular interaction between commercial hydrogels and drugs is not specific, the retention time of drug-soaked contact lenses is limited by their physical properties, mainly ionicity and water content [58]. Moreover, the drug pH should be kept between 6.6 to 9.0 to diminish ocular irritation and to control the dissolution of the drug at pH 7.4 to improve its diffusion through the cornea [74]. To improve both residence time and bioavailability of drugs, other specific methods to load drugs into contact lenses have been developed, such as functional monomers, molecular imprinting, colloidal nanoparticles, drug-polymer film embedding, and supercritical fluid, which will be detailed below. Maintaining the physical properties of polymers is very important for the manufacturing of soft contact lenses as drug delivery systems. The incorporation of functionalized compounds to hydrogels alters their oxygen permeability, water content, wettability, rigidity, flexibility, glass transition temperature, and light transmittance [58]. These parameters are critical because they affect comfort and visual quality during contact lens wear, compromising its safety and efficacy [75]. As an example of how physical properties can be altered, [PERSON] et al. [76] found that the incorporation of nanocapsules of prednisolone into soft contact lenses decreased their water content (between 4.7% and 5.5%), wettability (between 4.3\({}^{\circ}\) to 12.7\({}^{\circ}\) in terms of contact angle), rigidity (between 0.007 Mpa to 0.028 Mpa in terms of [PERSON]'s modulus), and light transmittance (between 8.3% and 11.4%). These alterations were directly proportional to the concentration of nanoparticles for some parameters, while for others there were no changes.