# In Vivo Efficacy of Contact Lens Drug-Delivery Systems in Glaucoma Management. A Systematic Review
## 3 Results
### Nanoparticle-Loaded CL  
Another CL drug-delivery technique was including drugs into nanoparticles that were incorporated inside the CL. Nanoparticles are defined as all particles having dimensions  
Figure 5: CL with multiple implants in the periphery, highlighted by red, green, and blue arrows. Reproduced with permission from [42], ©Copyright 2020, Elsevier. around or 10-1000 nm, such as liposomes or micelles, which acted as a carrier for the drug, although in some cases the drug itself was the nanoparticle [63]. The nanoparticles aimed to allow precise drug delivery with toxicity reduction and increased biocompatibility [63]. Nanoparticles allowed a high drug-loading capacity compared to a soaked CL. Furthermore, both hydrophilic and hydrophobic drugs could be loaded in the CL [63]. However, excessive nanoparticle loading could alter CL transparency [63]. Different nanoparticles were available--nanosuspension, nanodiamonds, nanocrystals, liposomes, niosomes, dendrimers, micelles, and cyclodext (Figure 6). [PERSON] et al. incorporated nanoparticles of propoxylated glyceryl triacrylate (PGT) containing timolol in a CL [43]. The CL was soaked in a solution of nanoparticles in ethanol. Then, the CL was applied continuously to dogs affected by OAG. The IOP lowered significantly for five days, although the therapeutic effect was detectable after day 2 of application. No adverse effects were reported. Interestingly, the authors compared a freshly soaked lens with a lens soaked and packaged for 15 days. The latter group showed a significantly reduced drug release rate, maybe related to the diffusion of the timolol-PGT particles into the packaging medium [43]. [PERSON] et al. developed a film of latanoprost and poly(lactic-co-glycolic) acid (PLGA) nanoparticle encapsulated in metafilcon by ultraviolet light polymerisation [44]. Then, the metafilcon block was lathed into the CL. This CL was continuously applied to glaucomatous rabbits for one month. Latanoprost was released for 28 days at a steady-state aqueous concentration significantly higher than the mean aqueous concentration with latanoprost eyedrops (\(p<0.05\)). However, on day one, the CL showed a drug concentration burst release higher than the one following latanoprost eyedrops instillation at 0.005% (854-1473 ng/mL versus 54 ng/mL). To reduce it, the latanoprost-eluting CL was soaked in phosphate-buffered saline for 1 or 3 days before the application. Both types of preconditioned CL showed a smaller initial burst (46-74 ng/mL) but a significantly reduced steady-state aqueous latanoprost concentration compared to the non-preconditioned version (5.5-5.7 ng/mL versus 21.0-39.6 ng/mL). It is essential to remark that latanoprost concentration was reported because it does not induce IOP-lowering in rabbits. In 25% of rabbits, the lenses moved slightly inferiorly, away from the corneal centre, and some of them developed limbal corneal neovascularization (exact percentage not reported) [44]. [PERSON] et al. also compared the latanoprost-PLGA CL to latanoprost eyedrops in glaucomatous monkeys [45]. Two versions of latanoprost-PLGA CL were developed, one with a high drug dose and one with a low drug dose. Each animal consecutively received the following treatment: eight days with the low-dose CL, eight days with latanoprost eyedrops, and eight days with the high-dose CL. The researchers observed a three-week washout period between different treatments. Only the high-dose CL showed a significantly greater IOP reduction than eyedrops at day 3 (\(p=0.001\)), day 5 (\(p=0.015\)), and day 8 (\(p<0.05\)). No adverse events were reported [45]. [PERSON] and colleagues developed an ethylcellulose-nanoparticle-laden ring loaded with the drug and installed it in a hydrogel CL [46]. This CL loaded with timolol was compared to timolol eyedrops in glaucomatous rabbits. The eyedrop group's IOP was  
Figure 6: Drug release from a CL loaded with nanostructures. Reproduced with permission from [53], @Copyright 2015, Elsevier.