Table 2.

Preparation of therapeutic contact lenses (CLs). AIBN: azobisisobutyronitrile; APMA: aminopropyl methacrylamide; β-CD: β-cyclodextrin; BEM: 2-butoxyethyl methacrylate; BSA: bovine serum albumin; DDAO: 7-Hydroxy- 9H-(1,3-dichloro-9,9- dimethylacridin-2-one); CMC: carboxymethyl chitosan; DEAA: N,N-diethylacrylamide; DMA: dimethylacryamide; DMPC: dimyristoyl phosphatidylcholine; EC: ethyl cellulose; EGDMA: ethylene glycol dimethacrylate; GMA: glycidyl methacrylate; GO: grapheme oxide; HEMA: poly (hydroxyethyl methacrylate); HPMC: hydroxypropyl methylcellulose; HTCC: N-[(2-hydroxy- 3-trimethylammonium) propyl] Chitosan Chloride; MAA: methacrylic acid; MMA: methylmethacrylate; NCs: nanocrystals; NPs: nanoparticles NVP: N-vinyl pyrrolidone; PEG-b-PCL: polyethylene glycol-block-polycaprolactone; PCL: polycaprolactone; PGT: propoxylated glyceryl triacrylate; PLGA: poly(lactide- co-glycolide); PMMA: poly (methyl methacrylate); P(MMAEHA-EGDMA): poly (methylmethacrylate-coethylhexylacrylate-co-ethyleneglycoldimethacrylate); PVA: polyvinyl alcohol; rAAV: recombinant adeno-associated virus; SiMA: 1-(tristrimethyl-siloxysilylpropyl)- methacrylate.

Drug-Loading Method	Polymeric Support	Active Principle	Application	Outcome	Ref.
Soaking method	Polyurethane film produced by solvent casting	Brimonidine tartrate	Glaucoma	Prolonged drug release up to 14 days	[38]
Drug-loaded liposomes by hydration method; soaking method	Lipids-based film	Besifloxacin hydrochloride	Conjunctivitis	Biphasic release: initial burst + sustained (80% released in 10 h)	[39]
-	DMA film placed on commercial CLs loaded with AIBN	Loading of vitamin E	-	AIBN release in about 30 min	[40]
Solvent casting	PLGA film embedded in methafilcon hydrogel- based CLs	Dexamethasone	Retinal diseases, such as diabetic macular edema	Prolonged drug release up to 160 h	[30]
Solvent casting	PLGA film embedded in HEMA hydrogel-based CLs	Ciprofloxacin	Post-operative treatment	Prolonged drug release for 1 month	[27]
Solvent casting	PLGA film embedded in HEMA hydrogel-based CLs	Econazole	Fungal keratitis	Extended antifungal activity	[29]
Solvent casting	PLGA film embedded in methafilcon hydrogel- based CLs	Latanoprost	Glaucoma	Initial burst + sustained drug release for 1 month.	[31]
Solvent casting	PLGA film embedded in methafilcon hydrogel- based CLs	Latanoprost	Ocular hypertension, glaucoma	Sustained drug delivery as effective as eyedrops	[32]
Solvent casting	Hydrogel-based CLs	Voriconazole loaded into GO; HTCC and silver nanoparticles as antimicrobial agents	Fungal Keratitis	Good antifungal and antimicrobial activity	[43]
Soaking or mixing method	PVA/collagen membrane	Ciprofloxacin hydrochloride, tobramycin	Ulcerative keratitis	Antibacterial activity for 48 h	[42]
Soaking method	HEMA hydrogels with/without APMA	rAAV	Corneal gene therapy	Efficacy in transduction/ triggering cell proliferation	[44]
Soaking method	Silicone hydrogels	Levofloxacin, chlorhexidine, diclofenac, timolol	-	High burst in the release profiles, optimization of sterilization method	[33]
Soaking method	Hydrogels based on HEMA, silicone, NVP and MMA	HPMC	-	pH-sensitivite drug release	[28]
Soaking method	PEG-modified silicone hydrogel	Roscovitine	Retinoblastoma	Prolonged drug release	[34]
Soaking method	HEMA/β-CD- hyaluronan hydrogels	Diclofenac sodium	Conjunctivitis	Therapeutic effect for conjunctivitis	[45]
Soaking method	Commercial hydrogel- based CLs	Voriconazole, diclofenac sodium	Acanthamoeba keratitis	Sustained release, cell proliferation	[46]
Soaking method	HEMA hydrogel- based CLs	Triamcinolone acetonide	Allergy	Prolonged drug release	[47]
Soaking method	Commercial HEMA hydrogel- based CLs	Timolol maleate	-	High-burst: 95% of drug released in 2 h	[48]
Soaking method from a solution or microemulsion	CLs based on siloxane, DMA, EGDMA, HEMA, Irgacure	Bimatoprost	Glaucoma	Microemulsion better than solution to prolong release	[20]
Soaking method	Commercial CLs based on silicone or HEMA hydrogels	Tetracaine, bupivacaine, ketotifen, diclofenac, flurbiprofen; loading of fatty acids (i.e., oleic acid, linoleic, α-linolenic acid)	-	Prolonged drug release, with an initial burst in the range 30–90% depending on the drug/CLs system	[49]
Soaking method	Commercial silicone hydrogel CLs	Timolol maleate; loading of vitamin E	Ocular hypertension, glaucoma	High drug bioavailability, reduction of hypertension	[35]
Soaking method	HEMA-based hydrogels with EGDMA, GMA, NVP, AIBN	Alexa Fluor 488 dye, brimonidine, timolol; loading of vitamin E and A	Glaucoma	Increase in drug loading, drug release in 6 h	[50]
Soaking method	Commercial silicone hydrogel CLs	Fluconazole, dexamethasone, timolol maleate; vitamin E loading	Eye inflammation, glaucoma	Prolonged drug release, beneficial effect of blocking UV radiation	[36]
Soaking method	Commercial CLs based on senofilcon A	Timolol maleate, dorzolamide hydrochloride; vitamin E loading	Glaucoma	Prolonged drug release	[51]
Soaking method	Commercial silicone hydrogel CLs	Dexamethasone; vitamin E loading	Eye inflammation	Prolonged drug release	[52]
Drug/BSA NCs by acid-base neutralization reactions; soaking method	NCs based on BSA and loaded into HEMA hydrogels	Meloxicam	Ocular irritation, antophthalmia after cataract surgery	Reduction of eye irritation, extended drug release	[53]
Drug-loaded micelles by thin-film hydration method	PEG-b-PCL micelles (with a PCL core and silica shell) loaded into HEMA hydrogels	Dexamethasone	Chronic posterior segment eye diseases	Prolonged drug release up to 30 days	[54]
-	PEG-b-PCL micelles into HEMA hydrogels	DDAO dye	-	Extended release for at least 14 days	[23]
Drug-loaded liposomes placed on CLs by multilayer immobilization; soaking method	Commercial CLs	Levofloxacin	Bacterial infections, such as keratitis	Antibacterial activity against Staphylococcus aureus	[55]
Drug-laden liposomes loaded into hydrogels by free radical solution polymerization	DMPC liposomes loaded into HEMA-hydrogel CLs	Lidocaine	-	Drug release prolonged for about 7 days	[56]
Drug-loaded lipid NPs by melt-emulsification and ultrasonication method; soaking	Compritol 888 ATO and triglyceride as lipid carriers for NPs soaked into hydrogels based on CMC and poloxamer 407	Quercetin	-	Improvement in drug transcorneal penetration and the precorneal retention time	[37]
Drug/PGT NPs by thermal polymerization; soaking method	PGT-based NPs loaded into commercial silicone hydrogel CLs	Timolol maleate	Ocular hypertension, glaucoma	Prolonged drug release, reduction in hypertension, optimization of storage conditions	[57]
Drug/silica NPs by microemulsion	Drug/silica shell NPs loaded into HEMA-based hydrogels	Lidocaine	Glaucoma	Prolonged drug release kinetics, with a 50% burst effect	[4]
Drug/Eudragit NPs by quasi-emulsion solvent diffusion; soaking for direct- drug-loaded CLs	pH-sensitive drug/Eudragit S100 NPs laden into hydrogel CLs	Cyclosporine	Chronic dry eyes syndrome	Prolonged drug release up to 14 h, no leaching after packaging	[19]
Drug/silica NPs by microemulsion; direct-drug-loaded CLs by free radical polymerization	Drug/silica shell NPs loaded into hydrogels based on HEMA, MAA, EGDMA	Ketotifen fumarate	Allergy	Reduced loss in transmittance and physical properties of hydrogels with NPs by emultion	[21]
Drug-loaded EC NPs by double emulsion	Drug/EC NPs into ring implants based on HEMA, EGDMA and MAA, then incorporated into hydrogel CLs	Timolol maleate	Glaucoma	Sustained drug release and reduction in intraocular pressure (for 170 h /190 h)	[25]
Soaking method	CLs based on HEMA, DMA, EGDMA, NVP, siloxane and Irgacure	Timolol maleate, gold NPs	-	Rapid drug release in a few hours, reduction in intraocular pressure	[58]
Soaking method	Drug-loaded semi-circular rings based on HEMA, MAA, EGDMA and Irgacure D, then implanted into hydrogel CLs	Moxifloxacin HCl, hyaluronic acid	Conjunctivitis	Improvement in drug residence time, bactericidal activity, optimization of sterilization method	[26]
Cast moulding	Drug- loaded semi-circular acrylate rings implanted in CLs	Timolol maleate, hyaluronic acid	Glaucoma	High burst in drug release, optimization of sterilization	[59]
Solvent casting for drug-loaded implants; soaking method for direct-drug-loaded CLs	Silicone CLs; implants based on Irgacure, EGDMA, DMA, NVP, siloxane, HEMA, then embedded into silicone CLs	Bimatoprost, hyaluronic acid, timolol	Ocular hypertension, glaucoma	High burst effect in drug release profiles	[24]
Molecular imprinting	Hydrogels based on HEMA, DEAA, DMA, SiMA, MMA	Timolol maleate	Glaucoma	Fast release, increase in drug loading by imprinting	[22]
Molecular imprinting	Hydrogels based on HEMA, EGDMA, MAA, AIBN	Acyclovir, valacyclovir hydrochloride	Herpes simplex virus ocular keratitis	High drug loadings	[60]
Soaking method; supercritical impregnation	Commercial hydrogel CLs based on Methafilcon A, Nelfilcon A, Omafilcon A, Hilafilcon B	Flurbiprofene, timolol maleate	Glaucoma	Higher drug loadings with shorter process times by sup. impregnation	[61]
Soaking method; supercritical impregnation	Foldable acrylic hydrogel CLs, based on HEMA and BEM with MAA and acrylamide	Norfloxacin	Cataract	Higher drug loadings by supercritical impregnation	[62]
Supercritical impregnation	Commercial silicone CLs based on Hilafilcon B	Salicylic acid	-	Prolonged drug release for 8 h	[63]
Supercritical impregnation	Commercial rigid CLs based on PMMA	Cefuroxime sodium	Cataract	Prolonged drug release for 15 days	[64]
Supercritical impregnation	Commercial silicone hydrogel CLs, based on Balafilcon A	Acetazolamide, timolol maleate	Glaucoma	Higher drug loadings	[65]
Supercritical impregnation	Foldable acrylic CLs, based on HEMA	Dexamethasone, ciprofloxacin	Cataract	Prolonged drug release for 60 days	[66]
Supercritical impregnation	Commercial foldable acrylic CLs	Gatifloxacin	Endophthalmitis after cataract surgery	Imrpovement in impregnation yield	[67]
Supercritical impregnation	P(MMA-EHA-EGDMA) films	Flurbiprofen	Eye surgery	Prolonged drug released in 3 months	[68]
Supercritical impregnation	Commercial foldable acrylic CLs	Methotrexate	Posterior capsule opacification after cataract surgery	Prolonged drug release for more than 100 days, inhibition of fibrosis	[69]
Supercritical impregnation	Commercial silicone CLs, based on Balafilcon A	Acetazolamide	Glaucoma	Fast drug release in about 3 h	[70]
Supercritical impregnation	Commercial rigid CLs based on PMMA	Dexamethasone, ciprofloxacin	Prevention of short- and mid-term postoperative complications	Prolonged drug release up to about 40 days	[71]
Supercritical CO2- assisted molecular imprinting	Commercial silicone CLs	Flurbiprofen	-	Prolonged drug release up to about 8 h	[72]