Purpose: To analyze the release of two fluoroquinolones, ciprofloxacin and moxifloxacin, from conventional hydrogel (CH) and silicone hydrogel (SH) daily disposable contact lenses (CLs), comparing release from a fixed-volume vial and an in vitro eye model. Methods: Four CH CLs (nelfilcon A, omafilcon A, etafilcon A, ocufilcon B) and three SH CLs (somofilcon A, narafilcon A, delefilcon A) were used. The lenses were incubated in drug solutions for 24 h. After the incubation period, the lenses were placed in two release conditions: (1) a vial containing 4.8 mL of PBS for 24 h and (2) an in vitro eye model with a flow rate at 4.8 mL over 24 h. Results: Release in the vial for both drugs was rapid, reaching a plateau between 15 min and 2 h for all lenses. In contrast, under physiological flow conditions, a constant and slow release was observed over 24 h. The amounts of ciprofloxacin released from the lenses ranged between 49.6±0.7 to 62.8±0.3 µg/lens in the vial, and between 35.0±7.0 to 109.0±5.0 µg/lens in the eye model. Moxifloxacin release ranged from 24.0±4.0 to 226.0±2.0 µg/lens for the vial, and between 13.0±2.0 to 151.0±10.0 µg/lens in the eye model. In both systems and for both drugs, HEMA-based CLs released more drugs than other materials. Conclusions: The parameters of the release system, in particular the volume and flow rate, have a significant influence on measured release profiles. Under physiological flow, release profiles are significantly slower and constant when compared with release in a vial.
1 November 2016 in Translational Vision Science & Technology
Purpose: The aim of this study was to evaluate and compare the release of moxifloxacin from a variety of daily disposable (DD) contact lenses (CLs) under various conditions using a novel in vitro eye model. Methods: Four commercially available DD conventional hydrogel (CH) CLs (nelfilcon A, omafilcon A, etafilcon A, and ocufilcon B) and three silicone hydrogel (SH) CLs (somofilcon A, narafilcon A, and delefilcon A) were evaluated. These lenses were incubated in moxifloxacin for 24 hours. The release of the drug was measured using a novel in vitro model in three experimental conditions: (1) phosphate buffered saline (PBS); (2) artificial tear solution (ATS) containing a variety of proteins and lipids; and (3) ATS with mechanical rubbing produced by the device. Results: Overall, CH CLs had a higher drug release than SH CLs (P < 0.05) under all conditions. Typically, a higher drug release was observed in PBS than ATS (P < 0.05). For CH, drug release was found to be higher in ATS with rubbing than PBS or ATS (P < 0.05). For most lens types, ATS with rubbing produced higher drug release than ATS alone (P < 0.05). Generally, the release kinetics for all conditions were sustained over the 24-hour testing period, and no burst release was observed (P < 0.05). Conclusions: Moxifloxacin release from a CL into ATS is lower when compared to release into PBS. When mechanical rubbing is introduced, the amount of drugs released is increased. Translational Relevance: Results suggest that sophisticated in vitro models are necessary to adequately model on-eye drug release from CL materials.
Continuous glucose monitoring aims to achieve accurate control of blood glucose concentration to prevent hypo/hyperglycaemia in diabetic patients. Hydrogel-based systems have emerged as a reusable sensing platform to quantify biomarkers in high-risk patients at clinical and point-of-care settings. The capability to integrate hydrogel-based systems with optical transducers will provide quantitative and colorimetric measurements via spectrophotometric analyses of biomarkers. Here, we created an imprinting method to rapidly produce 2.5D photonic concavities in phenylboronic acid functionalized hydrogel films. Our method exploited diffraction properties of hexagonally-packed 2.5D photonic microscale concavities having a lattice spacing of 3.3 μm. Illumination of the 2.5D hexagonally-packed structure with a monochromatic light source in transmission mode allowed reversible and quantitative measurements of variation in the glucose concentration based on first order lattice interspace tracking. Reversible covalent phenylboronic acid coupling with cis-diols of glucose molecules expanded the hydrogel matrix by ∼2% and 34% in the presence of glucose concentrations of 1 mM and 200 mM, respectively. A Donnan osmotic pressure induced volumetric expansion of the hydrogel matrix due to increasing glucose concentrations (1–200 mM), resulted in a nanoscale modulation of the lattice interspace, and shifted the diffraction angle (∼45° to 36°) as well as the interspacing between the 1st order diffraction spots (∼8 to 3 mm). The sensor exhibited a maximum lattice spacing diffraction shift within a response time of 15 min in a reversible manner. The developed 2.5D photonic sensors may have application in medical point-of-care diagnostics, implantable chips, and wearable continuous glucose monitoring devices.
The purpose of this study was to investigate the release of the anti-myopia drugs atropine sulfate and pirenzepine dihydrochloride from commercially available soft contact lenses. Standard ultraviolet (UV) absorbance–concentration curves were generated for atropine and pirenzepine. Ten commercially available contact lenses, including four multifocal lenses, were loaded by soaking in atropine or pirenzepine solutions at two different concentrations (10 mg/mL and 1 mg/mL). The release of the drugs into phosphate-buffered saline was determined over the course of 24 hours at 34°C using UV absorbance. Materials with surface charge released the greatest amount of atropine when loaded with either concentration when compared to the other lens types (p<0.05), releasing upward of 1.026±0.035 mg/lens and 0.979±0.024 mg/lens from etafilcon A and ocufilcon A, respectively. There were no significant differences in the amount of atropine or pirenzepine released from the multifocal and non-multifocal lenses made from the same lens materials. Narafilcon A material demonstrated prolonged release of up to 8 hours when loaded with pirenzepine, although the overall dose delivered from the lens into the solution was among the lowest of the materials investigated. The rest of the lenses reached a plateau within 2 hours of release, suggesting that they were unable to sustain drug release into the solution for long periods of time. Given that no single method of myopia control has yet shown itself to be completely effective in preventing myopia progression, a combination of optical and pharmaceutical devices comprising a drug delivering contact lens presents a novel solution that warrants further investigation.
1 September 2016 in Eye & Contact Lens: Science & Clinical Practice
Purpose: To evaluate the effects of two commercial silicone hydrogel contact lenses (CLs) soaked with natamycin (NA) or fluconazole (FL) on the growth of Candida albicans in an in vitro eye model. Methods: Three-D printed molds were used as a cast for making eye-shaped models comprising potato dextrose agar. Senofilcon A (SA) and lotrafilcon B (LB) CLs were incubated with either 2 mL of NA or FL at a concentration of 1 mg/mL for 24 hr. To simulate a fungal infection, the eye models were coated with C. albicans. The drug-soaked lenses were placed on top of the eye models. Seven experimental conditions were examined: (1) NA-SA, (2) NA-LB, (3) FL-SA, (4) FL-LB, (5) SA, (6) LB, and (7) control—no lens. At specified time points (t=1, 8, 16, 24, 48 hr), the agar eyes from each experimental condition were removed from the incubator and photographed. The yeast cells from the 24 and 48 hr time point were also analyzed using light microscopy. Results: At 24 and 48 hr, there was considerable growth observed for all conditions except for the NA-SA and NA-LB conditions. When observed under the microscope at 24 and 48 hr, the morphology of the yeast cells in the FL-SA and SA condition were similar to that of the control (oval shaped). There was limited hyphae growth observed for LB and significant visible hyphae growth for the NA-LB group. For NA-SA, NA-LB, and FL-LB groups, the cells were significantly smaller compared with the control. Conclusions: For NA-SA and NA-LB, there was limited growth of C. albicans observed on the eye models even after 48 hr. Under the microscope, the cell morphology differ noticeably between each testing condition, and is dependent on drug-lens combinations.