Silicone-based Hydrogel Research Articles

Imprinted hydrogels with LbL coating for dual drug release from soft contact lenses materials

A combined strategy to control the release of two drugs, one anti-inflammatory (diclofenac sodium, DCF) and one antibiotic (moxifloxacin hydrochloride, MXF), from a soft contact lens (SCL) material, was assessed. The material was a silicone-based hydrogel, which was modified by molecular imprinting with MXF and coated by the layer-by-layer (LbL) method using natural polyelectrolytes: alginate (ALG), poly-l-lysine (PLL) and hyaluronate (HA), crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). Imprinting was used to increase the amount of MXF loaded and to sustain its release, while the LbL coating acted as a diffusion barrier for DCF and improved the surface properties. The drugs were loaded by soaking in a DCF + MXF dual solution. High hydrostatic pressure (HHP) was successfully applied in the sterilization of the drug-loaded hydrogels. The transmittance, refractive index, wettability and ionic permeability of the hydrogels remained within the required levels for SCLs application. The concentrations of the released DCF and MXF stayed above the IC50 and the MIC (for S. aureus and S. epidermidis) values, for 9 and 10 days, respectively. No ocular irritancy was detected by the HET-CAM test. NIH/3T3 cell viability demonstrated that the drug-loaded hydrogels were not toxic, and cell adhesion was reduced.

Moxifloxacin-imprinted silicone-based hydrogels as contact lens materials for extended drug release

Contact lenses may act as drug release platforms for the treatment of ocular infections, but there is still the need for extending their typical release periods and enhancing ocular bioavailability. The present study aimed to develop a molecularly imprinted silicone-based hydrogel to be used in the manufacturing of contact lenses that can be loaded efficiently and be able to release the antibiotic moxifloxacin hydrochloride (MXF) in a sustained way. A set of hydrogels was prepared by the molecular imprinting method using acrylic acid (AA) as the functional monomer for the specific recognition of MXF. The modified hydrogels loaded a higher amount of MXF, which was released for a longer time. In vitro experiments, using a microfluidic cell to mimic the ocular surface fluid turnover, showed that the imprinted hydrogel TRIS(300)-I prepared with the highest content in AA led to MXF concentrations in the release medium which were effective against S. aureus and S. epidermidis for about 2 weeks. Furthermore, some important properties such as water uptake, wettability, transmittance, ionic permeability, and Young´s modulus of the modified hydrogel remained within the range of values recommended for contact lenses. No cytotoxicity and no potential ocular irritancy effect were detected. Such hydrogel seems to be a promising alternative to the current options for the treatment of ocular infections.

Design of circular-ring film embedded contact lens for improved compatibility and sustained ocular drug delivery

Contact lenses are ideal medical devices to sustain the release of ophthalmic drugs. However, the incorporation of drug loaded system can cause visual obstruction and poor oxygen/light permeability which restrict the application of contact lens for long-term wearing. Inspired by the physiological structure of our human eyes, we assume a circular-ring type inner layer embedded CLs might be a good solution to address the above-mentioned problems. In this study, taking betaxolol hydrochloride (BH) as a model drug, its complex with ion exchange resin was used as a carrier for adjusting drug loading amount, which is being dispersed into circular-ring shape Eudragit® S100 film as an inner layer, silicone-based hydrogel as the outer layer. Influence of resin particle size and drug/S100 ratio on drug release profiles was investigated. It was demonstrated that using resin as a carrier can not only increase drug loading amount but also sustain drug release, with the drug release rate well-tuned by either changing particle size of the resin or S100 ratio. Meanwhile S100 can well function as a pH-triggered drug release matrix, with limited drug leakage in the storage medium. Light transmittance of over 97% was achieved in the novel circular-ring layer-embedded CLs. Oxygen permeability coefficient (Dk) of the circular-ring film embedded CLs was 31.1 ± 3.7 barrer, similar to that of pure CLs. The sustained drug release behavior of this circular-ring embedded CLs was also well demonstrated in vivo. A level A IVIVC between in vitro drug release and in vivo drug concentration in tear fluid of the circular-ring embedded CLs was established. In conclusion, this circular-ring embedded contact lens is very promising for ophthalmic drug delivery with enhanced compatibility, sustained and pH triggered drug release characteristics.

Diclofenac sustained release from sterilised soft contact lens materials using an optimised layer-by-layer coating.

A layer-by-layer (LbL) coating was designed using ionic polysaccharides (chitosan, sodium alginate, sodium hyaluronate) and genipin (crosslinker), to sustain the release of diclofenac sodium salt (DCF) from soft contact lens (SCL) materials. The coating was hydrophilic, biocompatible, non-toxic, reduced bacterial growth and had minor effects on the physical properties of the material, such as wettability, ionic permeability, refractive index and transmittance, which remained within the recommended values for SCLs. The coating was applied on a silicone-based hydrogel and on commercial SofLens and Purevision SCLs. The coating attenuated the initial drug burst and extended the therapeutic period for, at least, two weeks. Relevantly, the problems of sterilizing drug loaded SCLs coated with biopolymers, using classic methods that involve high temperature or radiation, were successfully solved through high hydrostatic pressure (HHP) sterilization.

Imprinted Hydrogels with LbL Coating for Dual Drug Release from Soft Contact Lenses Materials

A combined strategy to control the release of two drugs, one anti-inflammatory (diclofenac sodium, DCF) and one antibiotic (moxifloxacin hydrochloride, MXF), from a soft contact lens (SCL) material, was assessed. The material was a silicone-based hydrogel, which was modified by molecular imprinting with MXF and coated by the layer-by-layer (LbL) method using natural polyelectrolytes: alginate (ALG), poly-L-lysine (PLL) and hyaluronate (HA) hyaluronate), crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). Imprinting was used to increase the amount of MXF loaded and to sustain its release, while the LbL coating acted as a diffusion barrier for DCF and improved the surface properties. The drugs were loaded by soaking in a DCF+MXF dual solution. High hydrostatic pressure (HHP) was successfully applied in the sterilization of the drug-loaded hydrogels. The transmittance, refractive index, wettability and ionic permeability of the hydrogels remained within the required levels for SCLs application. The concentrations of the released DCF and MXF stayed above the IC50 and the MIC (for S. aureus and S. epidermidis) values, for 9 and 10 days, respectively. No ocular irritancy was detected by the HET-CAM test. NIH/3T3 cell viability demonstrated that the drug-loaded hydrogels were not toxic, and cell adhesion was reduced.

Synthesis and Characterization of Silicone Contact Lenses Based on TRIS-DMA-NVP-HEMA Hydrogels.

In this study, silicone-based hydrogel contact lenses were prepared by the polymerization of 3-(methacryloyloxy)propyltris(trimethylsiloxy)silane (TRIS), N,N-dimethylacrylamide (DMA), 1-vinyl-2-pyrrolidinone (NVP), and 2-hydroxyethylmethacrylate (HEMA). The properties of silicone hydrogel lenses were analyzed based on the methods such as equilibrium water content, oxygen permeability, optical transparency, contact angle, mechanical test, protein adsorption, and cell toxicity. The results showed that the TRIS content in all formulations increased the oxygen permeability and decreased the equilibrium water content, while both DMA and NVP contributed the hydrophilicity of the hydrogels. The maximum value of oxygen permeability was 74.9 barrers, corresponding to an equilibrium water content of 44.5% as well as a contact angle of 82°. Moreover, L929 fibroblasts grew on all these hydrogels, suggesting non-cytotoxicity. In general, the silicone hydrogels in this work exhibited good oxygen permeability, stiffness, and optical transparency as well as anti-protein adsorption. Hence, these silicone hydrogel polymers would be feasible for making contact lens.

Antibacterial layer-by-layer coatings to control drug release from soft contact lenses material

In this study we investigated the possibility of using polyelectrolytes with antibacterial properties to form layer-by-layer (LbL) coatings on contact lens materials with the objective of controlling the release of ophthalmic drugs, while minimizing bacterial growth. A silicone-based hydrogel recently proposed by our group was chosen as a drug releasing soft contact lens (SCL) material and three drugs were tested: moxifloxacin hydrochloride (MXF), chlorhexidine diacetate monohydrate (CHX), and diclofenac sodium salt (DIC). Employed coatings involved combinations of sodium alginate (ALG), chitosan (CHI), sodium hyaluronate (HA) and polylysine hydrobromide (PLL), using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) as a cross-linking agent. Controlled release of DIC was achieved using two double layers of the following combinations: ALG/PLL (EDC), HA (EDC)/CHI and HA/PLL (EDC) + Drug. Furthermore, the physical properties of the coated lens material were kept, or even improved, and bacterial growth was reduced. In contrast, these coatings did not retard the release of MXF and CHX. The specificity of the barrier effect of these LbL films for DIC may be attributed to the formation of reversible interactions between DIC and the polyelectrolyte chains. A top layer of HA was needed to reduce the interaction with tear proteins. The in vivo efficacy of a contact lens coated with ALG/PLL (EDC)//HA and loaded with DIC was predicted using a simplified mathematical model to estimate the drug concentration in the tear fluid. The period of time during which the estimated concentration of DIC remained above the half-maximum inhibitory concentrations for the active enzymes in the process of inflammation, was at least double that obtained with the uncoated sample.

Drug-eluting silicone hydrogel for therapeutic contact lenses: Impact of sterilization methods on the system performance

Although contact lenses are promising platforms for ocular drug delivery and have been extensively studied for that purpose, the influence of sterilization methods on these systems remains barely investigated. In this work, a silicone-based hydrogel was produced and loaded with different ophthalmic drugs: levofloxacin, chlorhexidine, diclofenac and timolol. The drug release profiles, along with several material properties, were evaluated before and after sterilization by three different methods steam heat, γ-irradiation and ozone gas. Independently of the sterilization method used, the results of the swelling and mechanical properties tests strongly indicate the occurrence of specific drug-polymer interactions promoted by the sterilization. In general, these interactions led to a decrease on the amount of drug released. It is shown that γ-irradiation and ozone led to significant degradation of all of the drugs used in this study. Thus, it was concluded that steam heat is the sterilization method with less impact on the devices. More importantly, the present work shows that the development of efficient and functional drug delivery devices for ophthalmic purposes cannot be done independently of a careful analysis of the influence of the sterilization procedures and methods on the degradation of these polymeric systems as a whole.

Chitosan/alginate based multilayers to control drug release from ophthalmic lens

In this study we investigated the possibility of using layer-by-layer deposition, based in natural polymers (chitosan and alginate), to control the release of different ophthalmic drugs from three types of lens materials: a silicone-based hydrogel recently proposed by our group as drug releasing soft contact lens (SCL) material and two commercially available materials: CI26Y for intraocular lens (IOLs) and Definitive 50 for SCLs. The optimised coating, consisting in one double layer of (alginate – CaCl2)/(chitosan+glyoxal) topped with a final alginate-CaCl2 layer to avoid chitosan degradation by tear fluid proteins, proved to have excellent features to control the release of the anti-inflammatory, diclofenac, while keeping or improving the physical properties of the lenses. The coating leads to a controlled release of diclofenac from SCL and IOL materials for, at least, one week. Due to its high hydrophilicity (water contact angle≈0) and biocompatibility, it should avoid the use of further surface treatments to enhance the useŕs comfort. However, the barrier effect of this coating is specific for diclofenac, giving evidence to the need of optimizing the chemical composition of the layers in view of the desired drug.

Improvement of the surface wettability of silicone hydrogel contact lenses via layer-by-layer self-assembly technique

The surface wettability and anti-protein adsorption of a silicone-based hydrogel that was synthesized by a block copolymer of polydimethylsiloxane (PDMS) and poly (ethylene glycol) methacrylate (PEGMA) was improved via polyelectrolyte multilayer (PEM) immobilization. Polysaccharide PEMs of chitosan (CS, as a positive-charged agent) and hyaluronic acid (HA, as a negative-charged and anti-adhesive agent) were successfully assembled on the PDMS-PU-PEGMA silicone hydrogel in a layer-by-layer (LBL) self-assembly manner. Atomic force microscopy (AFM) and dyeing data verified the progressive buildup of the PEM silicone hydrogel. The results showed that the contact angle of the silicone hydrogel decreased with an increase in the number of PEM grafting layers. Furthermore, after immobilizing five layers of CS/HA, the protein adsorption decreased from 78±11 to 26±4μg/cm2 for HSA and from 55±10 to 20±4μg/cm2 for lysozymes. This indicates that CS/HA PEM-immobilized silicone hydrogels can resist protein adsorption. Furthermore, these hydrogels were non-cytotoxic according to an in vitro L929 fibroblast assay. Overall, the results demonstrated that the modified silicone hydrogels exhibited hydrophilicity and anti-protein adsorption, as well as relatively high oxygen permeability and optical transparency. Therefore, they would be applicable as a contact lens material.

Novel silicone hydrogel based on PDMS and PEGMA for contact lens application

A silicone-based hydrogel was synthesized from poly(dimethylsiloxane) dialkanol (PDMS), isophorone diisocyanate (IPDI), 2-hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol) methacrylate (PEGMA). The hydrophilicity of the resulting block copolymer was adjustable by manipulating the ratio of PDMS and PEGMA. The results showed that higher PEGMA content led to a lower water contact angle, higher water content, lower elastic modulus and higher glucose permeability. At a PEGMA content of 20%, the protein adsorption decreased to 23% and 18% for lysozyme and human serum albumin (HSA), respectively, of those of the control (PDMS-PU). This indicated that the PDMS-PU–PEGMA hydrogels exhibited an ability to resist protein adsorption. The oxygen permeability (Dk) was 92 barrers for the hydrogel with 20% PEGMA. Furthermore, these hydrogels were non-cytotoxic according to an in vitro L929 fibroblast assay. Overall, the results demonstrated that the PDMS-PU–PEGMA hydrogels exhibited not only relatively high oxygen permeability and relative optical transparency, but also hydrophilicity and anti-protein adsorption; therefore, they would be applicable as a contact lens material. Furthermore, this study demonstrated a new approach to controlling the performance of silicone hydrogels.

Effect of plasma treatment on the performance of two drug-loaded hydrogel formulations for therapeutic contact lenses.

Although the plasma technology has long been applied to treat contact lenses, the effect of this treatment on the performance of drug-loaded contact lenses is still unclear. The objective of this work is to study the effect of nitrogen plasma treatment on two drug-loaded polymeric formulations which previously demonstrated to be suitable for therapeutic contact lenses: a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel loaded with levofloxacin and a silicone-based hydrogel loaded with chlorhexidine. Modifications of the surface and the optical properties, and alterations in the drug release profiles and possible losses of the antimicrobial activities of the drugs induced by the plasma treatment were assessed. The results showed that, depending on the system and on the processing conditions, the plasma treatment may be beneficial for increasing wettability and refractive index, without degrading the lens surface. From the point of view of drug delivery, plasma irradiation at moderate power (200 W) decreased the initial release rate and the amount of released drug, maintaining the drug activity. For lower (100 W) and higher powers (300 W), almost no effect was detected because the treatment was, respectively, too soft and too aggressive for the lens materials.

Dynamic contact angle analysis of silicone hydrogel contact lenses using the Wilhelmy plate technique

Purpose: The literature on the use of the Wilhelmy plate technique for the analysis of contact lenses is somewhat limited; there is perhaps only one paper which compared a range of contact lens materials using the technique. This is possibly due to complications associated with its use in the analysis of such materials. The aim of this work is to analyse a range of silicone-based hydrogel contact lens materials using the technique.

Anti-glaucoma drug-loaded contact lenses prepared using supercritical solvent impregnation

Post-processing drug impregnation of commercially available polymer-based devices is a recent and attractive approach for the development of multifunctional biomedical devices and implants, drug release systems and tissue scaffolds. Therapeutic ophthalmic articles, such as drug-loaded contact lenses, are already known to improve ocular bioavailability in the treatment of several eye diseases, namely glaucoma, as well as to minimize undesired systemic side-effects. In this work, commercial silicone-based hydrogel contact lenses (Balafilcon A) were impregnated with two anti-glaucoma drugs (acetazolamide and timolol maleate) using a discontinuous supercritical solvent impregnation (SSI) methodology. Pressure and temperature, as well as impregnation time and depressurization rate, were kept constant (17 MPa, 40 °C, 90 min, 0.06 MPa/min, respectively) in order to evaluate the effects of nature and concentration of cosolvents (ethanol and water at 5, 10 and 15% molar) on the impregnation efficiencies and the properties of the contact lenses. Glass-transition temperature (DSC), oxygen permeability, contact angle, apparent morphological changes (SEM) and in vitro drug release kinetics were studied in detail. Results demonstrated the feasibility of preparing acetazolamide and timolol maleate impregnated therapeutic Balafilcon A contact lenses using CO 2 + EtOH and CO 2 + H 2O solvent mixtures. Valuable information about how the nature and the composition of the employed solvent mixtures influence drug loading, drug release profiles and contact lenses physical and thermomechanical properties was obtained.

Micro-Raman spectroscopy of refractive index microstructures in silicone-based hydrogel polymers created by high-repetition-rate femtosecond laser micromachining

Micro-Raman spectroscopy was used to study silicone-based hydrogel polymers after being modified by 800 nm, 27 fs laser pulses from a Ti:sapphire oscillator at 93 MHz repetition rate. When the irradiation conditions were below the optical breakdown threshold of the polymers, no significant changes in the Raman spectra and background fluorescence were observed even when refractive index changes as large as +0.06±0.005 were observed. On the other hand, changes in the Raman spectra and fluorescence were easily detected when higher pulse energy was employed to induce visible optical damage in the hydrogel polymers. These results show that a significant refractive index modification, below the optical breakdown threshold in silicone-based hydrogel polymers, can be realized in the absence of any significant change in the Raman spectrum of polymer composition. A thermal model is presented to explain these results. It shows that high-repetition-rate laser pulses cause significant heat accumulation, which can induce additional cross-linking and densification in the polymer network, resulting in locally increased refractive index.

Femtosecond laser micromachining of waveguides in silicone-based hydrogel polymers

By tightly focusing 27 fs laser pulses from a Ti:sapphire oscillator with 1.3 nJ pulse energy at 93 MHz repetition rate, we are able to fabricate optical waveguides inside hydrogel polymers containing approximately 36% water by weight. A tapered lensed fiber is used to couple laser light at a wavelength of 632.8 nm into these waveguides within a water environment. Strong waveguiding is observed due to large refractive index changes. A large waveguide propagation loss is found, and we show that this is caused by surface roughness which can be reduced by optimizing the waveguides.