A Mussel-Inspired Facile Method to Prepare Multilayer-AgNP-Loaded Contact Lens for Early Treatment of Bacterial and Fungal Keratitis

Abstract

The use of contact lenses for the early treatment of bacterial or fungal keratitis has become a new research focus. Two main requirements of the therapeutic contact lenses are antimicrobial ability and visible light transmittance. Silver nanoparticles (AgNPs), as a nonspecific antimicrobial component, have been loaded onto contact lenses for the treatment of bacterial and fungal keratitis. Recently, it was reported that, via a simple immersion method, AgNPs can be synthesized and fixed onto the surface of polydopamine (PDA)-coated materials. However, in this study, we found that the above traditional method has the disadvantages of poor AgNP loading and low visible light transmittance, which could be induced by a limited amount of phenolic hydroxyl groups on and second oxidation of the PDA coating, respectively. To overcome these disadvantages, in this paper, we provided a facile and novel method to robustly bind multilayer-AgNPs on contact lens surfaces by using dopamine as a reducing agent and bioglue. In comparing with the monolayer-AgNP-loaded contact lenses fabricated by the traditional method, the multilayer-AgNP-loaded contact lenses had excellent antimicrobial ability and better visible light transmittance. Moreover, the multilayer-AgNP-loaded contact lens had low cytotoxicity to human corneal epithelial cells and anti-inflammation properties. Furthermore, the shortcoming of decreasing visible light transmittance induced by excess adherence of AgNPs on the multilayer-AgNP-loaded contact lens was alleviated by decreasing the size of AgNPs through altering the concentration of dopamine and AgNO3. Contact lenses loaded with small AgNPs (Ag@PDA-2.5, diameter ≈ 25–50 nm) had approximately the same Ag+ release and antimicrobial abilities, but significantly better visible light transmittance and anti-inflammatory properties than the contact lenses loaded with large AgNPs (Ag@PDA-5, diameter ≈ 50–75 nm). After that, in vivo testing indicated the promising therapeutic strategy of multilayer-AgNP-loaded contact lenses (Ag@PDA-2.5) for early bacterial keratitis and fungal keratitis. In addition, PDA coating could provide reactive sites to immobilize other biomolecules or drugs on this multilayer-AgNP-loaded contact lens for further combination therapies in treating bacterial or fungal keratitis. Finally, the stability of the visible light transmittance of the multilayer-AgNP-loaded contact lens was detected. The visible light transmittance of Ag@PDA-2.5 was weakened after being cultured with an extremely high concentration of bacteria, while it was stable in the moderate work environment. Though PDA coating had been wildly used to modify implantation devices, however, few studies about PDA coating modified contact lenses have been reported so far. Therefore, this research also provides an important basis for using PDA coating to modify a therapeutic contact lens.

Chitosan‐based nanocomposites for medical applications

“…Nanocomposite substrates offer additional properties such as antimicrobial or antifungal ones to avoid tissue damage from infection/inflammation, which is one of the key factors hindering tissue regeneration upon implantation of new tissue. 25 One advantage of chitosan is that its surface adsorbs proteins rapidly. 26 Several articles reviewed the biomedical applications of chitosan-based nanocomposites in suspensions like nanogels and micelles.…”

Facile coating of urinary catheter with bio–inspired antibacterial coating

“…Since the antibacterial activity of AgNPs coated catheter is dependent on the release of silver ions, time–dependent Ag + release from the PDA/AgNPs coated catheter was investigated at 37 °C using ICP analysis. Figure 3 illustrated that silver was released in a sustained manner with constant rate during the first seven days [37, 38]. The release rate was dependent on the density of AgNPs where a higher amount of Ag + was release from catheter treated with 10 mg ml −1 of AgNO 3 (PDA/Ag 10) compared with that traded with 5 mg ml −1 of AgNO 3 (PDA/Ag 5).…”

Therapeutic Ophthalmic Lenses: A Review

“…Promising new strategies have been suggested for a wider approach to the anterior segment pathologies, addressing, for example, neurotrophic keratitis, persistent epithelial defects, diabetic keratopathy, and diabetic neuropathy, such as the use of topical insulin, naltrexone, ARIs, substance P, and different growth factors [160,169,170,174,200]. Poly-ε-lysine [190] Antifungals CL Silicone hydrogel (N/A) [191,194] Poly-ε-lysine [193] HEMA-PC [194] HEMA-MAA [194] HEMA-MAA-PVP [189,194] Sil-DMA-HEMA-PVP [194] Quaternized chitosan + graphene oxide [192] Antivirals CL HEMA-MAA [195,196] Collagen photosensitizer Riboflavin CL HEMA-PVP [197,199,201] Sil-DMA [201] PVP-MMA [201] Opioid antagonist Naltrexone CL HEMA [87] [44,45] Naltrexone (NTX) is an opioid antagonist, whose systemic or topical administration proved to block the negative effect of opioid growth factors, which are excessively present in diabetic patients, on cell proliferation and tissue growth. The use of naltrexone eye drops resulted in an accelerated corneal wound healing and the restoration of corneal sensitivity in many animal models, and it is considered to be a promising treatment of diabetic keratopathy [160,174].…”

“…In recent years, several examples of the mentioned drugs have been incorporated into CLs using many different techniques, and the obtained results have been extensively discussed in previous review papers [ 21 , 111 , 186 ]. Therapeutic CLs for the treatment of keratitis have also been widely reported in literature reviews [ 187 , 188 ], with promising results for the delivery of biocides [ 189 , 190 ], antifungals [ 189 , 191 , 192 , 193 , 194 ], and antiviral drugs [ 195 , 196 ].…”