Novel Contact Lenses Embedded with Drug-Loaded Zwitterionic Nanogels for Extended Ophthalmic Drug Delivery  
[PERSON]  
1 School of Material Engineering, Jinling Institute of Technology, Nanjing 211169, China;  
[PERSON]ADDRESS] (XL. ); [EMAIL_ADDRESS] (X.Z. ); [PERSON]_ADDRESS] (Q.L. ); [EMAIL_ADDRESS] (W.S.) [PERSON]  
1 School of Material Engineering, Jinling Institute of Technology, Nanjing 211169, China;  
[PERSON]ADDRESS] (XL. ); [EMAIL_ADDRESS] (X.Z. ); [PERSON]_ADDRESS] (Q.L. ); [EMAIL_ADDRESS] (W.S.) [PERSON]  
1 School of Material Engineering, Jinling Institute of  
and burst release are prevalent problems, with complete drug release from the lens within a few hours. Recently, some innovative strategies, such as in situ creation of a vitamin E barrier [9], molecular imprinting technology [10], drug-laden nanoparticles, the introduction of ionic or 'host-guest' interactions [11] and the incorporation of drug-loaded polymer films [12] have been reported to achieve the continuous release of drugs [13; 14; 15; 16; 17; 18]. Although great efforts have been achieved in drug-eluting contact lenses, however, the critical lens properties, such as optical transparency, ion and oxygen permeability, mechanical durability, serialization and storage stability, as well as patient and practitioner acceptance have yet to be addressed [19]. Colloidal nanoparticles (nanogels, liposomes, micelles, microemulsions, etc.) have attracted great attention as drug delivery carriers because of their efficient drug loading and sustained-release properties [20; 21]. Incorporating drug-loaded nanocarriers into hydrogels will prolong the drug-release time [22; 23], for drugs need to release from the nanoparticles and then diffuse through the hydrogel matrix to reach the action site. Moreover, encapsulation of drugs in colloidal nanoparticles can prevent drug degradation by ocular enzymes. The drug release rate and targeted therapy can be further improved by the effective design of delivery vehicles. The mPEG-PCL micelle-laden contact lens prepared by [PERSON] et al. for the treatment of glaucoma achieved the sustained release of timolol and latanoprost in tears for more than four days [24]. [PERSON] et al. [25] recently prepared hyaluronic acid (HA)-loaded chitosan (CS) nanoparticles, which were dispersed in a ring shape poly(vinyl alcohol) (PVA) hydrogel to form the ring-implanted PVA contact lens. Results showed a sustained release of HA from the contact lens for treatment of dry eye syndrome for up to 14 days. A special contact lens made of Bri@LDH/Thermogel composite drug delivery system (DDS) developed by [PERSON] et al. [26] showed sustained biomidine release for up to 168 h, and effectively relieved intraocular pressure (IOP). Furthermore, in cyclosporine-loaded Eudragit S100 (pH-sensitive) nanoparticle-laden contact lenses designed by [PERSON] et al. [27], in vitro drug-release experiments showed no significant leaching of the drug during sterilization and the storage period (pH 6.5). At the same time, accelerated drug release was achieved in a tear environment (pH 7.4) because of the dissolution of Eudragit S100. [PERSON] et al. [28] also reported extended levobunolol release from pH-sensitive Eudragit nanoparticle-laden contact lenses for glaucoma therapy. However, the natural aggregation of nanoparticles reduced the optical transparency of contact lenses, and the decreased water content caused by the incorporation of nanoparticles reduced the wear comfort of the contact lenses. Nanogels are defined as hydrogel nanoparticles with sizes in the range of 1-1000 nm formed by physical or chemical cross-linking [29]. Nanogels are hydrophilic, flexible, highly water-absorbent, biocompatible, etc., and their size, charge, porosity, hydrophilicity, flexibility and degradability can be adjusted by changing the chemical composition of nanogels. They can load drugs, proteins or DNA efficiently via salt bridges, hydrogen bonds and/or hydrophobic interactions, and their large surface area facilitates the conjugation of multivalent biomolecules.