Smart contact lens systems for ocular drug delivery and therapy.

Ocular drug delivery and therapy systems have been extensively investigated with various methods including direct injections, eye drops and contact lenses. Nowadays, smart contact lens systems are attracting a lot of attention for ocular drug delivery and therapy due to their minimally invasive or non-invasive characteristics, highly enhanced drug permeation, high bioavailability, and on-demand drug delivery. Furthermore, smart contact lens systems can be used for direct light delivery into the eyes for biophotonic therapy replacing the use of drugs. Here, we review smart contact lens systems which can be classified into two groups of drug-eluting contact lens and ocular device contact lens. More specifically, this review covers smart contact lens systems with nanocomposite-laden systems, polymeric film-incorporated systems, micro and nanostructure systems, iontophoretic systems, electrochemical systems, and phototherapy systems for ocular drug delivery and therapy. After that, we discuss the future opportunities, challenges and perspectives of smart contact lens systems for ocular drug delivery and therapy.

Smart contact lens containing hyaluronate-rose bengal conjugate for biophotonic myopia vision correction.

As the collagen layer weakens with increasing age or certain diseases such as keratoconus and myopia, the mechanical property of the collagen layer decreases with corneal deformation. To circumvent these problems, the corneal collagen has been crosslinked with the photosensitizer riboflavin under UV light after de-epithelialization. However, this treatment with riboflavin and UV light can cause notable damage to the eye. Here, the biocompatible rose bengal (RB) dye was conjugated to hyaluronic acid (HA) to enhance the corneal permeability, which can be activated by safe green light with a wavelength of 530 nm. Two-photon microscopy revealed the deep tissue penetration of the HA-RB conjugate in comparison with RB. Collagen fibrillogenesis, ex vivo tensile test, and ex vivo histological analysis confirmed the effective collagen crosslinking by HA-RB conjugate and the light irradiation. Furthermore, we developed a smart contact lens for on-demand HA-RB conjugate delivery from the reservoir embedded in the contact lens. Taken together, we could envision the feasibility of a smart contact lens for biophotonic myopia vision correction.

Multispectral upconversion nanoparticles for near infrared encoding of wearable devices.

Individual recognition technology such as iris recognition and bar coding has been extensively investigated for non-face-to-face authorization. However, there are still strong unmet needs for facile, rapid, and robust individual recognition. Here, we developed multispectral transparent films of upconversion nanoparticles (UCNPs) for near-infrared (NIR) encoding of wearable devices including contact lenses and patch devices. A multispectral UCNP film in a contact lens showed various luminescence colors of patterns under 980 nm NIR light irradiation and each color could be assigned to a specific code by RGB value analysis. The encoded film of UCNPs in the contact lens was successfully decoded by the RGB value analysis with a charge coupled digital (CCD) camera. Furthermore, the UCNP barcode film could be applied in the form of attachable barcode patches onto various substrates like porcine skin and paper currency. Taken together, we could confirm the feasibility of multispectral UCNP transparent films as a facile individual recognition platform for non-face-to-face authorization.

Drug-eluting contact lens containing cyclosporine-loaded cholesterol-hyaluronate micelles for dry eye syndrome.

A contact lens is an attractive tool for the delivery of ophthalmic drugs, but it has several issues such as the burst release of drugs and the limited drug loading capacity. To overcome these limitations, we developed a cholesterol-hyaluronate (C-HA) micelle-embedded contact lens for efficient hydrophobic drug loading and long-term controlled drug delivery. The contact lens was fabricated via photopolymerization of hydroxyethyl methacrylate (HEMA) using ethylene glycol dimethacrylate (EGDMA) as a cross-linker. The C-HA micelle-loaded contact lens showed statistically significant improvement in wettability and mechanical strength, maintaining the optical transmittance. In vitro drug release tests revealed the controlled delivery of cyclosporine for more than 12 days. Furthermore, the Schirmer tear test, corneal fluorescein staining, and MMP9 fluorescein analysis confirmed its therapeutic effect on dry eye syndrome in disease model rabbits.

Hyaluronate-Gold Nanorod/DR5 Antibody Complex for Noninvasive Theranosis of Skin Cancer.

Noninvasive transdermal delivery is a promising method with distinct advantages including patient compliance over other delivery routes. Here, hyaluronate-gold nanorod/death receptor 5 antibody (HA-AuNR/DR5 Ab) complex was developed for transdermal theranosis of skin cancer. The successful formation of the complex was corroborated by 1H nuclear magnetic resonance, UV-vis spectroscopy, dynamic light scattering, zeta potential, and transmission electron microscopy. In vitro biological activity of the complex was verified by ELISA and MTT assay using HCT116 cancer cells. In addition, in vivo photoacoustic imaging and two-photon microscopy clearly visualized the transdermal delivery of HA-AuNR/DR5 Ab complex through the inevitable barrier of stratum corneum in the skin. Furthermore, in vivo antitumor effect on skin cancer model mice was confirmed from statistically significant decrease of tumor-reflecting luciferase expression levels and apoptotic signals in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Taken together, we could confirm the feasibility of HA-AuNR/DR5 Ab complex as a novel theranostic platform for noninvasive transdermal treatment of skin cancers.