# Modification of Silicone Hydrogel Contact Lenses with Vitamin E for the Delivery of Ofloxacin

Authors: Xiaojuan Zhang; Yuan Zhao; Yuyang Jing; Zhao Wang; Wenli Song; Dong Liang; Qing Lin
Journal: Journal of Nanomaterials
 (2023)

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## Abstract

This study synthesized silicone hydrogel (SHL) contact lenses modified by vitamin E (VE). First, the prepolymer GKF8010, methacryloxymethyltris (trimethylsiloxy) silane, andN,N-dimethylaniline were used to synthesize SHL contact lenses through ultraviolet irradiation by using ethylene glycol dimethacrylate as crosslinker. Then, VE was combined with SHL contact lenses (VE/SHL) in ethanol solution. The obtained SHL and VE/SHL contact lenses were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, transmittance analysis, contact angle test, mechanical property analysis, and dynamic mechanical thermal analysis. Compared with SHL contact lenses, VE/SHL contact lenses had a porous structure, good transmittance, hydrophobic properties, and mechanical properties. Ofloxacin (OFL) was loaded into SHL and VE/SHL contact lenses by the soaking method. The drug release, antibacterial, and biocompatibility properties were further characterized. VE/SHL-OFL contact lenses could deliver OFL at therapeutic doses for 5 days. The antibacterial test indicated that VE/SHL-OFL contact lenses displayed inhibition ring sizes of 8.14 and 16.66 mm for Escherichia coli and Staphylococcus aureus, respectively. Besides, cell viability assays showed that the obtained VE/SHL contact lenses were cytocompatible and might be potential drug carriers for oculopathy treatment.


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## Body

## 1. Introduction

With the rapid development of science and technology in today’s society, our life has become increasingly inseparable from electronic products. At the same time, corneal diseases, such as xerophthalmia and keratitis, are becoming increasingly serious in workers due to long-term exposure to computers. Corneal blindness is one of the main causes of blindness in China, and infectious keratitis is the main cause of blindness. At present, ophthalmic diseases are mostly treated with eye drops, which require repeated administration for 5–10 min. However, only 5% of the total drugs can work, and the rest can only be metabolized for circulation [1].Researchers used hydrogel materials as contact lenses for drug delivery [2]. Drug concentration can be obviously improved, and drug bioavailability is remarkably enhanced. At the same time, the systemic absorption of the drug can be avoided, and sustained drug delivery can be realized. Reports showed that contact lenses are carriers with high biocompatibility and controlled drug release [3]. Hydrogel contact lenses can maintain a certain shape and allow small molecules to permeate and diffuse. Compared with traditional hydrogel contact lenses, silicone hydrogel (SHL) contact lenses are soft and have high permeability and water content [4]. In addition, the mechanical properties of the material are enhanced by the addition of silicone. Nicolson and Vogt [6] suggested that SHL can be regarded as a composite material with different hydrogel and silicon phases, and each phase has a fixed property [5–9]. Given the soft texture, good biocompatibility, and easy acceptance by the human body, SHL contact lenses are the most widely used contact lenses [10–12].Many types of contact lenses, including nanoparticle-based [13], layer-structured [14], biomimetic [15], and imprinted [16] contact lenses, have been used to increase the release duration of drug. Vitamin E (VE) is a fat-soluble antioxidant that can inhibit keratocyte apoptosis after surgery and prevent glaucoma [17]. VE is introduced into hydrogel contact lenses to extend drug release due to its lipophilic barrier. Torres-Luna et al. [18] developed contact lenses loaded with VE and cationic surfactants to extend the delivery of anti-inflammatory drugs.Given that the long-term wearing of contact lenses causes microbial reproduction [19, 20] and infection [21–23], ofloxacin (OFL) [24] is selected as model antibiotic. VE is incorporated into SHL contact lenses to reduce the internal pore size and delivery of OFL, further explore the modification of VE in contact lenses, improve the properties of SHL contact lenses, and control drug release.


## 2. Experimental

### 2.1. Materials

Glycidyl methacrylate (GMA) and Darocur1173 were purchased from Sam Chemical Technology (Shanghai) Co. Ltd. Aminoalkyl-terminated polydimethylsiloxane (KF8010) was obtained from Shin-Etsu Chemical Co. Ltd. Anhydrous calcium chloride was obtained from Shanghai Fengxian Fengcheng Reagent Factory. Methacryloxymethyltris(trimethylsiloxy)silane (TRIS) andN,N-dimethylacrylamide (DMA) were purchased from Tokyo Chemical Industry. Ethylene glycol (EG) was obtained from Sinopharm Chemical Reagent Co. Ltd. VE was purchased from Sinopharm XingSha Pharmaceuticals Co. Ltd. OFL was obtained from Jiangsu the Yellow River Pharmaceutica Limited by Share Ltd.


### 2.2. Synthesis and Drug Loading of VE-Modified SHL (VE/SHL) Contact Lenses

First, 2.73 mL of GMA and 8.2047 g of KF 8010 were mixed in a flask at 80°C for 6 hr to obtain the prepolymer of GKF8010. Then, 1.455 g of GKF8010, 1.6 mL of TRIS, 0.242 g of Darocur1173, and 2 mL of DMA were mixed in a vial and then added to the flask. Then, the mixture was added with 0.3 mL of ethanol and 8 mg of EG dimethacrylate oxide, stirred for 10 min, and placed in a polytetrafluoroethylene mold. After UV irradiation for 10 min, SHL contact lenses were prepared and soaked in a VE–ethanol solution with different concentrations (20, 40, 60, and 80 mg·mL−1) overnight, and samples were labeled as VE-modified SHL (VE/SHL)-1, VE/SHL-2, VE/SHL-3, and VE/SHL-4, respectively. After their full expansion, VE/SHL contact lenses were collected and naturally dried. The amount of VE in the hydrogel was determined by air drying the lens, and the weights of SHL and SHL/VE contact lenses were measured. The content of VE in the hydrogel is listed in Table 1.Table 1
Content of VE in the hydrogel.
Concentration of VE (mg·mL−1)Amount of VE/SHL (g)Amount of VE (g)Content of VE in the hydrogel (wt%)VE/SHL-1200.09640.006887.14VE/SHL-2400.09330.007748.30VE/SHL-3600.08360.0086010.29VE/SHL-4800.08320.0094611.37The prepared SHL and VE/SHL-3 contact lenses were placed in OFL solution with different concentrations (0.1 and 0.2 mg·mL−1), and the mixture was oscillated at a constant temperature of 25°C for 24 hr. Then, OFL-SHL and VE/SHL-3-OFL contact lenses were obtained. The loading of OFL and release process in VE/SHL-3-OFL contact lenses are shown in Figure 1. The chemical structure of SHL is shown in Figure 2.Figure 1
OFL loading and release process in VE-modified silicone hydrogel contact lenses (VE/SHL-3-OFL).Figure 2
Chemical structure of SHL.


### 2.3. Fourier Transform Infrared (FTIR) Spectroscopy, Scanning Electron Microscopy (SEM), X-Ray Photoeclectron Spectroscopy (XPS), and Transmittance and Contact Angle Analyses

The Thermo NICOLET iS10 spectrometer was used to obtain the infrared spectrum of hydrogel contact lenses. The Hitachi Model S-4800 microscope was used to observe the morphology of contact lenses. The surface elemental composition of samples was characterized by X-ray photoeclectron spectroscopy (XPS) (Escalab250Xi). Ultraviolet–visible (UV–vis) spectrophotometry (Gainuvled-LAB100-40) was used to measure the transmittance of SHL and VE/SHL-3 in the wavelength range of 300–750 nm. A contact angle meter (Kruss-DSA25) was used to test the contact angles of contact lenses.


### 2.4. Saturated Moisture Content

SHL was placed in normal saline and kept at 15, 30, 45, 60, and 75°C. After 24 hr, SHL contact lenses were collected and dried, and the weight was recorded asW1. Subsequently, SHL contact lenses were subjected to vacuum drying at 80°C for 3 hr and collected, and the weight was recorded as W2. The saturated moisture content of VE/SHL-3 contact lenses was determined by the same method. The saturated moisture content was calculated using Equation (1):(1)SMC=W1−W2W1×100%.


### 2.5. Mechanical Properties

A universal testing machine (Instron, Model 5943) was used to test the mechanical properties of SHL and VE/SHL, and the crosshead speed was 10 mm·min−1 at room temperature. SHL and VE/SHL contact lenses were synthesized with dimensions of 20 mm × 12 mm × 1.8 mm. The dynamic mechanical analyzer Q800 was used to measure the dynamic mechanical thermal property. The experiment was carried out in the temperature range of 30–160°C in multifrequency–strain mode. A heating rate of 5°C·min−1 and frequency of 1 Hz were maintained to conduct this investigation.


### 2.6. Drug Release

Drug-release experiments were carried out by soaking SHL or VE/SHL-3 contact lenses loaded with different OFL concentrations in PBS (pH 7.4) at room temperature under gentle shaking. After removing 2 mL of the released sample at regular time intervals, 4 mL of PBS was added into the release medium [25]. A UV–vis spectrophotometer (Evolution 220, Thermo Fisher) was used to calculate the amount of drug released in accordance with the calibration curve of OFL in PBS at 289 nm. The relationship between absorbance (Abs) and drug concentration (C) can be described by Equation (2). Encapsulation and drug loading efficiencies were calculated using Equation (3), respectively.(2)A=65.1449C+0.07868,R2=0.9427.(3)Encapsulationefficiency=mdm0×100%,Drugloadingefficiency=mdmt×100%,where md is the mass of OFL in the SHL or VE/SHL-3, mt is the total mass of SHL or VE/SHL-3 contact lenses, and m0 is the total mass of OFL.


### 2.7. Antibacterial Study

The antibacterial activities of SHL and VE/SHL-3 contact lenses were tested usingStaphylococcus aureus and Escherichia coli [26]. SHL and VE/SHL-3 contact lenses were sterilized and cut to obtain a round sample with diameter of 0.54 cm by using the Muller–Hinton agar as culture medium. SHL, VE/SHL-3, and drug-sensitive papers (i.e., streptomycin and cefixime) were spread onto the culture medium and evenly coated with bacteria. After culturing for 24 hr, the inhibition zone surrounding each sample was measured to test the antibacterial effect.


### 2.8. In Vitro Cytotoxicity Assays

SIRC rabbit normal corneal epithelial cells (RNCECs) were used to assess the cytotoxicity of SHL and VE/SHL-3 contact lenses by the cell counting kit-8 (CCK8) assay. SHL and VE/SHL contact lenses were immersed in 75% aqueous alcohol for 4 hr and washed with PBS. After placing SHL and VE/SHL-3 contact lenses on the bottom surface of a 24-well plate, RNCECs were sequentially seeded onto the plate. The culture medium was incubated for 1, 2, 3, and 4 days, replaced by CCK-8, and incubated for 1 hr. Then, the Multiskan FC enzyme-labeled equipment (Thermo Scientific, USA) was used to test the absorbance atλ = 289 nm. Furthermore, the Olympus CKX41 fluorescence microscope was used to test living cells on day 3.


## 2.1. Materials

Glycidyl methacrylate (GMA) and Darocur1173 were purchased from Sam Chemical Technology (Shanghai) Co. Ltd. Aminoalkyl-terminated polydimethylsiloxane (KF8010) was obtained from Shin-Etsu Chemical Co. Ltd. Anhydrous calcium chloride was obtained from Shanghai Fengxian Fengcheng Reagent Factory. Methacryloxymethyltris(trimethylsiloxy)silane (TRIS) andN,N-dimethylacrylamide (DMA) were purchased from Tokyo Chemical Industry. Ethylene glycol (EG) was obtained from Sinopharm Chemical Reagent Co. Ltd. VE was purchased from Sinopharm XingSha Pharmaceuticals Co. Ltd. OFL was obtained from Jiangsu the Yellow River Pharmaceutica Limited by Share Ltd.


## 2.2. Synthesis and Drug Loading of VE-Modified SHL (VE/SHL) Contact Lenses

First, 2.73 mL of GMA and 8.2047 g of KF 8010 were mixed in a flask at 80°C for 6 hr to obtain the prepolymer of GKF8010. Then, 1.455 g of GKF8010, 1.6 mL of TRIS, 0.242 g of Darocur1173, and 2 mL of DMA were mixed in a vial and then added to the flask. Then, the mixture was added with 0.3 mL of ethanol and 8 mg of EG dimethacrylate oxide, stirred for 10 min, and placed in a polytetrafluoroethylene mold. After UV irradiation for 10 min, SHL contact lenses were prepared and soaked in a VE–ethanol solution with different concentrations (20, 40, 60, and 80 mg·mL−1) overnight, and samples were labeled as VE-modified SHL (VE/SHL)-1, VE/SHL-2, VE/SHL-3, and VE/SHL-4, respectively. After their full expansion, VE/SHL contact lenses were collected and naturally dried. The amount of VE in the hydrogel was determined by air drying the lens, and the weights of SHL and SHL/VE contact lenses were measured. The content of VE in the hydrogel is listed in Table 1.Table 1
Content of VE in the hydrogel.
Concentration of VE (mg·mL−1)Amount of VE/SHL (g)Amount of VE (g)Content of VE in the hydrogel (wt%)VE/SHL-1200.09640.006887.14VE/SHL-2400.09330.007748.30VE/SHL-3600.08360.0086010.29VE/SHL-4800.08320.0094611.37The prepared SHL and VE/SHL-3 contact lenses were placed in OFL solution with different concentrations (0.1 and 0.2 mg·mL−1), and the mixture was oscillated at a constant temperature of 25°C for 24 hr. Then, OFL-SHL and VE/SHL-3-OFL contact lenses were obtained. The loading of OFL and release process in VE/SHL-3-OFL contact lenses are shown in Figure 1. The chemical structure of SHL is shown in Figure 2.Figure 1
OFL loading and release process in VE-modified silicone hydrogel contact lenses (VE/SHL-3-OFL).Figure 2
Chemical structure of SHL.


## 2.3. Fourier Transform Infrared (FTIR) Spectroscopy, Scanning Electron Microscopy (SEM), X-Ray Photoeclectron Spectroscopy (XPS), and Transmittance and Contact Angle Analyses

The Thermo NICOLET iS10 spectrometer was used to obtain the infrared spectrum of hydrogel contact lenses. The Hitachi Model S-4800 microscope was used to observe the morphology of contact lenses. The surface elemental composition of samples was characterized by X-ray photoeclectron spectroscopy (XPS) (Escalab250Xi). Ultraviolet–visible (UV–vis) spectrophotometry (Gainuvled-LAB100-40) was used to measure the transmittance of SHL and VE/SHL-3 in the wavelength range of 300–750 nm. A contact angle meter (Kruss-DSA25) was used to test the contact angles of contact lenses.


## 2.4. Saturated Moisture Content

SHL was placed in normal saline and kept at 15, 30, 45, 60, and 75°C. After 24 hr, SHL contact lenses were collected and dried, and the weight was recorded asW1. Subsequently, SHL contact lenses were subjected to vacuum drying at 80°C for 3 hr and collected, and the weight was recorded as W2. The saturated moisture content of VE/SHL-3 contact lenses was determined by the same method. The saturated moisture content was calculated using Equation (1):(1)SMC=W1−W2W1×100%.


## 2.5. Mechanical Properties

A universal testing machine (Instron, Model 5943) was used to test the mechanical properties of SHL and VE/SHL, and the crosshead speed was 10 mm·min−1 at room temperature. SHL and VE/SHL contact lenses were synthesized with dimensions of 20 mm × 12 mm × 1.8 mm. The dynamic mechanical analyzer Q800 was used to measure the dynamic mechanical thermal property. The experiment was carried out in the temperature range of 30–160°C in multifrequency–strain mode. A heating rate of 5°C·min−1 and frequency of 1 Hz were maintained to conduct this investigation.


## 2.6. Drug Release

Drug-release experiments were carried out by soaking SHL or VE/SHL-3 contact lenses loaded with different OFL concentrations in PBS (pH 7.4) at room temperature under gentle shaking. After removing 2 mL of the released sample at regular time intervals, 4 mL of PBS was added into the release medium [25]. A UV–vis spectrophotometer (Evolution 220, Thermo Fisher) was used to calculate the amount of drug released in accordance with the calibration curve of OFL in PBS at 289 nm. The relationship between absorbance (Abs) and drug concentration (C) can be described by Equation (2). Encapsulation and drug loading efficiencies were calculated using Equation (3), respectively.(2)A=65.1449C+0.07868,R2=0.9427.(3)Encapsulationefficiency=mdm0×100%,Drugloadingefficiency=mdmt×100%,where md is the mass of OFL in the SHL or VE/SHL-3, mt is the total mass of SHL or VE/SHL-3 contact lenses, and m0 is the total mass of OFL.


## 2.7. Antibacterial Study

The antibacterial activities of SHL and VE/SHL-3 contact lenses were tested usingStaphylococcus aureus and Escherichia coli [26]. SHL and VE/SHL-3 contact lenses were sterilized and cut to obtain a round sample with diameter of 0.54 cm by using the Muller–Hinton agar as culture medium. SHL, VE/SHL-3, and drug-sensitive papers (i.e., streptomycin and cefixime) were spread onto the culture medium and evenly coated with bacteria. After culturing for 24 hr, the inhibition zone surrounding each sample was measured to test the antibacterial effect.


## 2.8. In Vitro Cytotoxicity Assays

SIRC rabbit normal corneal epithelial cells (RNCECs) were used to assess the cytotoxicity of SHL and VE/SHL-3 contact lenses by the cell counting kit-8 (CCK8) assay. SHL and VE/SHL contact lenses were immersed in 75% aqueous alcohol for 4 hr and washed with PBS. After placing SHL and VE/SHL-3 contact lenses on the bottom surface of a 24-well plate, RNCECs were sequentially seeded onto the plate. The culture medium was incubated for 1, 2, 3, and 4 days, replaced by CCK-8, and incubated for 1 hr. Then, the Multiskan FC enzyme-labeled equipment (Thermo Scientific, USA) was used to test the absorbance atλ = 289 nm. Furthermore, the Olympus CKX41 fluorescence microscope was used to test living cells on day 3.


## 3. Results and Discussion

### 3.1. FTIR Spectroscopy

The FTIR spectra of SHL and VE/SHL contact lenses are shown in Figure3. As shown in Figure 3(a), the peak at 3,450 cm−1 was ascribed to the –OH bond [27]. The peaks at 2,944, 1,417, and 1,261 cm−1 could be ascribed to the stretching vibration of Si-CH3. The peaks at 1,730 and 1,640 cm−1 could be ascribed to the C=O and N–H bonds, respectively [28]. The stretching vibration of –Si–O–Si– band in Tris was observed at 1,050 cm−1 [29]. Results indicated that SHL contact lenses were successfully synthesized by UV irradiation polymerization. As shown in Figure 3(b), the peak of DMA at 1,640 cm−1 shifted to 1,635 cm−1 after modification with VE, which was due to the hydrophilic interaction between VE and DMA unit of the polymer network in SHL [30].Figure 3
FTIR spectra of (a) SHL and (b) VE/SHL-3 contact lenses.


### 3.2. Morphology of SHL and VE/SHL

As shown in Figure4(a), SHL contact lenses were spherical and had good gloss. After VE modification, VE/SHL contact lenses still had intact spherical structure and decreased gloss (Figure 4(b)). SEM was used to observe the morphology of SHL and VE/SHL contact lenses (Figure 5). SHL contact lenses (Figure 5(a)) showed a porous structure made up of siloxane and hydrogel material [31]. As shown in Figure 5(b), the surface of VE/SHL-3 contact lenses exhibited a 3D porous structure, and the addition of appropriate VE (10.29 wt%) affected the interior morphology of the SHL. After adding 11.37 wt% VE, VE/SHL-4 contact lenses (Figure 5(c)) had decreased porous structure. Thus, the addition of excessive hydrophobic VE components into the system decreased hydrophilicity and porosity.Figure 4
Images of (a) SHL and (b) VE/SHL-3 contact lenses.
(a)(b)Figure 5
SEM images of (a) SHL, (b) VE/SHL-3, and (d) VE/SHL-4 contact lenses.
(a)(b)(c)


### 3.3. X-Ray Photoeclectron Spectroscopy

The surface compositions of SHL and VE/SHL-3 contact lenses were investigated by XPS. The elemental compositions (%) on the surfaces of SHL and VE/SHL-3 contact lenses determined by XPS are listed in Table2. Figures 6(a) and 6(b) exhibit the XPS survey spectra of SHL and VE/SHL-3 contact lenses, respectively. For SHL materials, the Si 2s and Si 2p photopeaks were evident along with prominent C1s and O1s peaks, and a small amount of N was observed (Figure 6(a)). After surface modification with VE, VE/SHL-3 contact lenses had increasingly evident C1s peaks. These atoms were located in the carbon chain in VE, which was also proven by the elemental composition in Table 2. C and O elemental contents were 56.83% and 24.09% in SHL contact lenses, and 69.49 and 18.48% in VE/SHL-3 contact lenses.Figure 6
XPS survey spectra of (a) SHL and (b) VE/SHL-3 contact lenses.
(a)(b)Table 2
Elemental compositions (%) of SHL and VE/SHL contact lenses.
SampleElement (%)COSiNSHL56.8324.0915.223.86VE/SHL-369.4918.4810.081.96


### 3.4. Transmittance

Figure7 exhibits that the transmittance curves of SHL and VE/SHL-3 contact lenses in the visible range were 97.1% and 98.4%, respectively. These results were over the international standard, i.e., 90% [32]. SHL contact lenses after VE modification maintained good transmittance.Figure 7
Transmittance curves of (a) SHL and (b) VE/SHL-3 contact lenses.


### 3.5. Contact Angle Analysis

The contact angles of SHL and VE/SHL-3 contact lenses were 104° ± 0.2° and 106° ± 0.7°, respectively. The contact angle of VE/SHL-3 contact lenses was higher than that of SHL contact lenses, which indicated that the modification of VE decreased the hydrophilicity of SHL contact lenses. This finding was due to the hydrophobicity of VE, which affected the wettability of the contact lenses’ surface.


### 3.6. Saturated Water Content

Figure8 presents the saturated water contents of (a) SHL and (b) VE/SHL-3 contact lenses over temperature. Within the range of 15–45°C, the saturated water content first increased and then decreased. At 45–75°C, the saturated water content increased with increasing temperature. This finding was predominantly related to the activity of hydrogen bonds and molecular chains between hydrophilic groups and water molecules in the SHL contact lenses’ network structure. At low temperature, the activity of the molecular chain was low, and the pores in the network structure of SHL were small, which led to minimal water molecules that could be stored. With increasing temperature, the activity of the polymer chain increased, and the pores of SHL increased, which resulted in increased water molecules that could be stored. The comparison showed that the saturated water content of VE/SHL-3 contact lenses was lower than that of SHL contact lenses. Part of the pores of VE/SHL-3 contact lenses was filled with VE, resulting in smaller pores and less saturated water content than SHL contact lenses.Figure 8
Saturated water contents of (a) SHL and (b) VE/SHL-3 contact lenses.


### 3.7. Mechanical Property Analysis

Figure9 exhibits the strain–stress curves of SHL and VE/SHL contact lenses. The tensile strength and elongation at break of SHL and VE/SHL are listed in Table 3. Figure 9(a) shows that the tensile strength and elongation at break of SHL contact lenses were 0.19 MPa and 32%, respectively. Figure 9(b) exhibits the tensile strength and elongation at break of VE/SHL-1 contact lenses were 0.170 MPa and 56%, respectively. As shown in Figure 9(c), the tensile strength and elongation at break of VE/SHL-2 contact lenses were 0.174 MPa and 53%, respectively. Figure 9(d) shows that VE/SHL-3 contact lenses had lower tensile strength (0.165 MPa) and higher elongation at break (51%) than SHL contact lenses. However, after adding 80 mg·mL−1 VE, VE/SHL-4 contact lenses had the lowest tensile strength and elongation at break. Thus, after adding VE with appropriate amount, SHL became soft and elastic because of the rearrangement of molecular chains in SHL [33].Figure 9
Strain–stress curves of (a) SHL, (b) VE/SHL-1, (c) VE/SHL-2, (d) VE/SHL-3, and (e) VE/SHL-4 contact lenses.Table 3
Tensile strength and elongation at break of SHL and VE/SHL contact lenses.
Tensile strength (MPa)Elongation at break (%)Content of VE in the hydrogel (wt%)SHL0.190320VE/SHL-10.170567.14VE/SHL-20.174538.30VE/SHL-30.1655110.29VE/SHL-40.1352511.37The variations in storage moduli of (a) SHL and (b) 30% VE/SHL contact lenses with temperature are exhibited in Figure10. Figure 10(a) shows that the storage modulus of SHL contact lenses decreased from 13.11 to 1.81 MPa when the temperature was increased from 30 to 100°C. The decrease in storage modulus was attributed to increased polymer chain mobility [34]. As shown in Figure 10(b), the storage modulus of VE/SHL-3 contact lenses decreased from 3.78 to 1.88 MPa when the temperature was increased from 30 to 100°C, and these values were lower than those of SHL contact lenses at 30 and 100°C. VE could be used as a diluent for controlling the modulus of contact lenses [35].Figure 10
Variations in storage and loss moduli of (a) SHL and (b) VE/SHL-3 contact lenses with varying temperature.
(a)(b)The loss modulus, which can measure the heat energy dissipation about the deformation of material, reveals the viscosity of materials. With increasing temperature from 30 to 100°C, the loss modulus of SHL contact lenses decreased from 5.58 to 0.02 MPa. The loss modulus of VE/SHL-3 contact lenses decreased from 1.22 to 0.03 MPa with increasing temperature from 30 to 100°C. Thus, the SHL with high loss modulus had higher restriction. Additionally, SHL contact lenses showed higher thermal stability than VE/SHL-3 contact lenses [35].


### 3.8. Drug Release

The release profiles of OFL from SHL and VE/SHL-3 contact lenses under different concentrations of OFL are shown in Figure11. The standard curve of OFL could be derived using Equation (3). The drug loading and encapsulation efficiencies of SHL contact lenses were 10.44% and 58.00%, respectively, and those of VE/SHL-3 contact lenses were 13.54% and 75.22%, respectively.Figure 11
Release behaviors of OFL from (a) SHL-OFL and (b) VE/SHL-3-OFL contact lenses with different OFL concentrations (0.1, 0.2, 0.3, and 0.4 wt%).
(a)(b)As shown in Figure11(a), with increasing concentration of OFL from 0.1 to 0.4 wt%, the cumulative release of OFL increased from 10.20% to 42.88%. When the concentration of OFL was 0.4 wt%, in the first 7 hr, an initial burst release of ∼30.65% could be observed. This phenomenon was ascribed to the diffusion of the drug adsorbed on the surface of the SHL. After 96 hr, the cumulative release continued and reached 42.88%. Thus, OFL release was driven by diffusion mechanism through the swollen polymeric network [36]. The rapid release occurred only in several hours with 0.2%–0.4% of OFL, which was attributed to the loose binding of OFL in the polymer matrix in “soak and release” lenses [37].After VE modification, the cumulative release of OFL increased from 19.77% to 88.23% with increasing concentration of OFL from 0.1 to 0.4 wt% (Figure11(b)). When the concentration of OFL was 0.4 wt%, VE/SHL-3 contact lenses exhibited a burst OFL release of more than 50% at 5 hr followed by slow release up to 56 hr and a cumulative drug release of 88.23% after 120 hr. The fast drug release in VE/SHL-3 contact lenses was predominantly driven by physical diffusion because of the drug concentration gradient inside and outside the hydrogel matrix. The release time of VE/SHL-3 contact lenses was extended from 96 to 120 hr. Thus, VE was absorbed in the pores of the network, hindered drug release, and prolonged the release time of OFL. In addition, the increase in release time because of VE incorporation was due to the barrier effect, i.e., OFL was forced to diffuse around the barriers, resulting in increased release time [38].


### 3.9. Antibacterial Properties

The antibacterial properties of (A) cefotaxime (CTX30), (B) streptomycin (S10), (C) VE/SHL contact lenses, and (D) VE/SHL-OFL contact lenses were studied for positiveE. coli (Figure 12(a)) and negative S. aureus (Figure 12(b)) through the disk diffusion method. Figure 12(A) shows that the control (cefotaxime) displayed inhibition ring sizes of 26.07 and 24.03 mm for E. coli and S. aureus, respectively. Figure 12(B) exhibits that streptomycin had inhibition ring sizes of 7.87 and 6.62 mm for E. coli and S. aureus, respectively. As shown in Figure 12(C), VE/SHL-3 contact lenses exhibited growth inhibition ring sizes of 7.88 and 0.6 mm for S. aureus and E. coli, respectively. Figure 12(D) reveals that VE/SHL-3-OFL contact lenses after loading with OFL had inhibition ring sizes of 8.14 and 16.66 mm for E. coli and S. aureus, respectively. The minimum bactericidal concentration of OFL in VE/SHL-3-OFL contact lenses for E. coli and S. aureus were 1 and 0.5 mg·mL−1. VE/SHL-3 contact lenses exhibited good antibacterial activities against E. coli and S. aureus, and this finding was ascribed to the efficient release of OFL in the media.Figure 12
Antibacterial activity screening images of (A) cefotaxime (CTX30), (B) streptomycin (S10), (C) VE/SHL-3 contact lenses, and (D) VE/SHL-3-OFL contact lenses against (a)E. coli and (b) S. aureus.
(a)(b)


### 3.10. In Vitro Cytotoxicity Assay

Cell viability data (Figure13) indicated that SHL and VE/SHL-3 contact lenses posed no considerable cytotoxicity to RNCECs. SHL and VE/SHL-3 contact lenses achieved ∼100% viability after 4 days of incubation. Fluorescence microscopy confirmed the cell viability results. The largest number of viable cells was observed in the control group (Figure 14(a)). After adding SHL and VE/SHL-3 contact lenses, RNCECs displayed no evident morphological change (Figures 14(b) and 14(c)). Therefore, SHL and VE/SHL-3 contact lenses exhibited good biocompatibility with RNCEC, indicating their suitability for eye disease treatment.Figure 13
Histogram of cell viability of (a) control, (b) SHL, and (c) VE/SHL-3 contact lenses in culture media.Figure 14
RNCECs on (a) control, (b) SHL, and (c) VE/SHL-3 contact lenses observed by fluorescence microscopy.
(a)(b)(c)


## 3.1. FTIR Spectroscopy

The FTIR spectra of SHL and VE/SHL contact lenses are shown in Figure3. As shown in Figure 3(a), the peak at 3,450 cm−1 was ascribed to the –OH bond [27]. The peaks at 2,944, 1,417, and 1,261 cm−1 could be ascribed to the stretching vibration of Si-CH3. The peaks at 1,730 and 1,640 cm−1 could be ascribed to the C=O and N–H bonds, respectively [28]. The stretching vibration of –Si–O–Si– band in Tris was observed at 1,050 cm−1 [29]. Results indicated that SHL contact lenses were successfully synthesized by UV irradiation polymerization. As shown in Figure 3(b), the peak of DMA at 1,640 cm−1 shifted to 1,635 cm−1 after modification with VE, which was due to the hydrophilic interaction between VE and DMA unit of the polymer network in SHL [30].Figure 3
FTIR spectra of (a) SHL and (b) VE/SHL-3 contact lenses.


## 3.2. Morphology of SHL and VE/SHL

As shown in Figure4(a), SHL contact lenses were spherical and had good gloss. After VE modification, VE/SHL contact lenses still had intact spherical structure and decreased gloss (Figure 4(b)). SEM was used to observe the morphology of SHL and VE/SHL contact lenses (Figure 5). SHL contact lenses (Figure 5(a)) showed a porous structure made up of siloxane and hydrogel material [31]. As shown in Figure 5(b), the surface of VE/SHL-3 contact lenses exhibited a 3D porous structure, and the addition of appropriate VE (10.29 wt%) affected the interior morphology of the SHL. After adding 11.37 wt% VE, VE/SHL-4 contact lenses (Figure 5(c)) had decreased porous structure. Thus, the addition of excessive hydrophobic VE components into the system decreased hydrophilicity and porosity.Figure 4
Images of (a) SHL and (b) VE/SHL-3 contact lenses.
(a)(b)Figure 5
SEM images of (a) SHL, (b) VE/SHL-3, and (d) VE/SHL-4 contact lenses.
(a)(b)(c)


## 3.3. X-Ray Photoeclectron Spectroscopy

The surface compositions of SHL and VE/SHL-3 contact lenses were investigated by XPS. The elemental compositions (%) on the surfaces of SHL and VE/SHL-3 contact lenses determined by XPS are listed in Table2. Figures 6(a) and 6(b) exhibit the XPS survey spectra of SHL and VE/SHL-3 contact lenses, respectively. For SHL materials, the Si 2s and Si 2p photopeaks were evident along with prominent C1s and O1s peaks, and a small amount of N was observed (Figure 6(a)). After surface modification with VE, VE/SHL-3 contact lenses had increasingly evident C1s peaks. These atoms were located in the carbon chain in VE, which was also proven by the elemental composition in Table 2. C and O elemental contents were 56.83% and 24.09% in SHL contact lenses, and 69.49 and 18.48% in VE/SHL-3 contact lenses.Figure 6
XPS survey spectra of (a) SHL and (b) VE/SHL-3 contact lenses.
(a)(b)Table 2
Elemental compositions (%) of SHL and VE/SHL contact lenses.
SampleElement (%)COSiNSHL56.8324.0915.223.86VE/SHL-369.4918.4810.081.96


## 3.4. Transmittance

Figure7 exhibits that the transmittance curves of SHL and VE/SHL-3 contact lenses in the visible range were 97.1% and 98.4%, respectively. These results were over the international standard, i.e., 90% [32]. SHL contact lenses after VE modification maintained good transmittance.Figure 7
Transmittance curves of (a) SHL and (b) VE/SHL-3 contact lenses.


## 3.5. Contact Angle Analysis

The contact angles of SHL and VE/SHL-3 contact lenses were 104° ± 0.2° and 106° ± 0.7°, respectively. The contact angle of VE/SHL-3 contact lenses was higher than that of SHL contact lenses, which indicated that the modification of VE decreased the hydrophilicity of SHL contact lenses. This finding was due to the hydrophobicity of VE, which affected the wettability of the contact lenses’ surface.


## 3.6. Saturated Water Content

Figure8 presents the saturated water contents of (a) SHL and (b) VE/SHL-3 contact lenses over temperature. Within the range of 15–45°C, the saturated water content first increased and then decreased. At 45–75°C, the saturated water content increased with increasing temperature. This finding was predominantly related to the activity of hydrogen bonds and molecular chains between hydrophilic groups and water molecules in the SHL contact lenses’ network structure. At low temperature, the activity of the molecular chain was low, and the pores in the network structure of SHL were small, which led to minimal water molecules that could be stored. With increasing temperature, the activity of the polymer chain increased, and the pores of SHL increased, which resulted in increased water molecules that could be stored. The comparison showed that the saturated water content of VE/SHL-3 contact lenses was lower than that of SHL contact lenses. Part of the pores of VE/SHL-3 contact lenses was filled with VE, resulting in smaller pores and less saturated water content than SHL contact lenses.Figure 8
Saturated water contents of (a) SHL and (b) VE/SHL-3 contact lenses.


## 3.7. Mechanical Property Analysis

Figure9 exhibits the strain–stress curves of SHL and VE/SHL contact lenses. The tensile strength and elongation at break of SHL and VE/SHL are listed in Table 3. Figure 9(a) shows that the tensile strength and elongation at break of SHL contact lenses were 0.19 MPa and 32%, respectively. Figure 9(b) exhibits the tensile strength and elongation at break of VE/SHL-1 contact lenses were 0.170 MPa and 56%, respectively. As shown in Figure 9(c), the tensile strength and elongation at break of VE/SHL-2 contact lenses were 0.174 MPa and 53%, respectively. Figure 9(d) shows that VE/SHL-3 contact lenses had lower tensile strength (0.165 MPa) and higher elongation at break (51%) than SHL contact lenses. However, after adding 80 mg·mL−1 VE, VE/SHL-4 contact lenses had the lowest tensile strength and elongation at break. Thus, after adding VE with appropriate amount, SHL became soft and elastic because of the rearrangement of molecular chains in SHL [33].Figure 9
Strain–stress curves of (a) SHL, (b) VE/SHL-1, (c) VE/SHL-2, (d) VE/SHL-3, and (e) VE/SHL-4 contact lenses.Table 3
Tensile strength and elongation at break of SHL and VE/SHL contact lenses.
Tensile strength (MPa)Elongation at break (%)Content of VE in the hydrogel (wt%)SHL0.190320VE/SHL-10.170567.14VE/SHL-20.174538.30VE/SHL-30.1655110.29VE/SHL-40.1352511.37The variations in storage moduli of (a) SHL and (b) 30% VE/SHL contact lenses with temperature are exhibited in Figure10. Figure 10(a) shows that the storage modulus of SHL contact lenses decreased from 13.11 to 1.81 MPa when the temperature was increased from 30 to 100°C. The decrease in storage modulus was attributed to increased polymer chain mobility [34]. As shown in Figure 10(b), the storage modulus of VE/SHL-3 contact lenses decreased from 3.78 to 1.88 MPa when the temperature was increased from 30 to 100°C, and these values were lower than those of SHL contact lenses at 30 and 100°C. VE could be used as a diluent for controlling the modulus of contact lenses [35].Figure 10
Variations in storage and loss moduli of (a) SHL and (b) VE/SHL-3 contact lenses with varying temperature.
(a)(b)The loss modulus, which can measure the heat energy dissipation about the deformation of material, reveals the viscosity of materials. With increasing temperature from 30 to 100°C, the loss modulus of SHL contact lenses decreased from 5.58 to 0.02 MPa. The loss modulus of VE/SHL-3 contact lenses decreased from 1.22 to 0.03 MPa with increasing temperature from 30 to 100°C. Thus, the SHL with high loss modulus had higher restriction. Additionally, SHL contact lenses showed higher thermal stability than VE/SHL-3 contact lenses [35].


## 3.8. Drug Release

The release profiles of OFL from SHL and VE/SHL-3 contact lenses under different concentrations of OFL are shown in Figure11. The standard curve of OFL could be derived using Equation (3). The drug loading and encapsulation efficiencies of SHL contact lenses were 10.44% and 58.00%, respectively, and those of VE/SHL-3 contact lenses were 13.54% and 75.22%, respectively.Figure 11
Release behaviors of OFL from (a) SHL-OFL and (b) VE/SHL-3-OFL contact lenses with different OFL concentrations (0.1, 0.2, 0.3, and 0.4 wt%).
(a)(b)As shown in Figure11(a), with increasing concentration of OFL from 0.1 to 0.4 wt%, the cumulative release of OFL increased from 10.20% to 42.88%. When the concentration of OFL was 0.4 wt%, in the first 7 hr, an initial burst release of ∼30.65% could be observed. This phenomenon was ascribed to the diffusion of the drug adsorbed on the surface of the SHL. After 96 hr, the cumulative release continued and reached 42.88%. Thus, OFL release was driven by diffusion mechanism through the swollen polymeric network [36]. The rapid release occurred only in several hours with 0.2%–0.4% of OFL, which was attributed to the loose binding of OFL in the polymer matrix in “soak and release” lenses [37].After VE modification, the cumulative release of OFL increased from 19.77% to 88.23% with increasing concentration of OFL from 0.1 to 0.4 wt% (Figure11(b)). When the concentration of OFL was 0.4 wt%, VE/SHL-3 contact lenses exhibited a burst OFL release of more than 50% at 5 hr followed by slow release up to 56 hr and a cumulative drug release of 88.23% after 120 hr. The fast drug release in VE/SHL-3 contact lenses was predominantly driven by physical diffusion because of the drug concentration gradient inside and outside the hydrogel matrix. The release time of VE/SHL-3 contact lenses was extended from 96 to 120 hr. Thus, VE was absorbed in the pores of the network, hindered drug release, and prolonged the release time of OFL. In addition, the increase in release time because of VE incorporation was due to the barrier effect, i.e., OFL was forced to diffuse around the barriers, resulting in increased release time [38].


## 3.9. Antibacterial Properties

The antibacterial properties of (A) cefotaxime (CTX30), (B) streptomycin (S10), (C) VE/SHL contact lenses, and (D) VE/SHL-OFL contact lenses were studied for positiveE. coli (Figure 12(a)) and negative S. aureus (Figure 12(b)) through the disk diffusion method. Figure 12(A) shows that the control (cefotaxime) displayed inhibition ring sizes of 26.07 and 24.03 mm for E. coli and S. aureus, respectively. Figure 12(B) exhibits that streptomycin had inhibition ring sizes of 7.87 and 6.62 mm for E. coli and S. aureus, respectively. As shown in Figure 12(C), VE/SHL-3 contact lenses exhibited growth inhibition ring sizes of 7.88 and 0.6 mm for S. aureus and E. coli, respectively. Figure 12(D) reveals that VE/SHL-3-OFL contact lenses after loading with OFL had inhibition ring sizes of 8.14 and 16.66 mm for E. coli and S. aureus, respectively. The minimum bactericidal concentration of OFL in VE/SHL-3-OFL contact lenses for E. coli and S. aureus were 1 and 0.5 mg·mL−1. VE/SHL-3 contact lenses exhibited good antibacterial activities against E. coli and S. aureus, and this finding was ascribed to the efficient release of OFL in the media.Figure 12
Antibacterial activity screening images of (A) cefotaxime (CTX30), (B) streptomycin (S10), (C) VE/SHL-3 contact lenses, and (D) VE/SHL-3-OFL contact lenses against (a)E. coli and (b) S. aureus.
(a)(b)


## 3.10. In Vitro Cytotoxicity Assay

Cell viability data (Figure13) indicated that SHL and VE/SHL-3 contact lenses posed no considerable cytotoxicity to RNCECs. SHL and VE/SHL-3 contact lenses achieved ∼100% viability after 4 days of incubation. Fluorescence microscopy confirmed the cell viability results. The largest number of viable cells was observed in the control group (Figure 14(a)). After adding SHL and VE/SHL-3 contact lenses, RNCECs displayed no evident morphological change (Figures 14(b) and 14(c)). Therefore, SHL and VE/SHL-3 contact lenses exhibited good biocompatibility with RNCEC, indicating their suitability for eye disease treatment.Figure 13
Histogram of cell viability of (a) control, (b) SHL, and (c) VE/SHL-3 contact lenses in culture media.Figure 14
RNCECs on (a) control, (b) SHL, and (c) VE/SHL-3 contact lenses observed by fluorescence microscopy.
(a)(b)(c)


## 4. Conclusion

VE was successfully introduced to modify SHL contact lenses, and the effects of VE on the properties were studied. SEM showed that the addition of VE led to decreased porous structure of VE/SHL contact lenses because VE decreased hydrophilicity and porosity. The evaluation of light transmittance, water contact angle, saturated water content, and mechanical properties exhibited that VE/SHL contact lenses maintained good comprehensive properties. Drug-release experiments revealed sustained OFL release in the therapeutic range for 5 days. Furthermore, VE/SHL-OFL contact lenses exhibited good antibacterial properties againstS. aureus and E. coli. Cell viability assay and morphological observations showed that SHL and VE/SHL contact lenses were cytocompatible. VE/SHL-OFL contact lenses have potential application in eye disease treatment.



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*Source: 1500048-2023-02-09.xml*