Alex Hui

Uptake and release of ciprofloxacin-HCl from conventional and silicone hydrogel contact lens materials.

Objectives. To investigate the uptake and release characteristics of the antibiotic ciprofloxacin-HCl in conventional and silicone hydrogel lenses, and evaluate their potential as therapeutic drug delivery devices. Methods. Nine differing soft contact lens materials were soaked in a 0.3% ciprofloxacin-HCl solution at 34°C. The uptake of the drug into the lenses was measured by the change in concentration over 24 hours using fluorescence spectrophotometry. The lenses were then placed in a buffered saline solution, and the release of the drug from the lenses was also measured using spectrophotometry. Results. The release of drug varied from 0.016 ± 0.004 mg/lens for lotrafilcon A lenses to 0.42 ± 0.03 mg/lens for etafilcon A lenses, with an average of 0.133 mg/lens. The 3 conventional lenses used in the study released a statistically significantly different amount of drug when compared with the silicone hydrogels. The release of drug was very rapid, with drug release reaching a plateau after no more than 10 minutes for the majority of the lenses. The majority of the lenses were able to release enough drug to achieve minimum inhibitory concentration 90 for most resistant ocular pathogens. Ciprofloxacin was found to heavily precipitate on the etafilcon A lenses during the release phase at physiologic pH. Conclusion. While balafilcon A released the most drug from the silicone hydrogel materials, all materials released the drug too quickly to be effective as drug delivery devices.

Uptake and release of dexamethasone phosphate from silicone hydrogel and group I, II, and IV hydrogel contact lenses.

Objectives To investigate the uptake and release kinetics of the synthetic glucocorticoid anti-inflammatory drug dexamethasone into various conventional and silicone hydrogel contact lens materials. Methods Three conventional and six silicone hydrogel lenses were used in this study. A 0.1% dexamethasone solution was formulated and used to dope the various contact lens materials. The uptake and release of the drug was measured using a UV-visible light spectrophotometer at various time points during a period of 24 hr for each phase. Results Statistical analysis showed that all lenses took up a significant amount of dexamethasone. Alphafilcon A and lotrafilcon A showed the greatest uptake of dexamethasone, at 118 ± 10 &mgr;g/lens and 102 ± 11 &mgr;g/lens, respectively, and galyfilcon took up the least amount of drug at 34 ± 6 &mgr;g/lens. The release of the drug from the lens materials was also statistically significant. The majority of the lenses released between 20 and 30 &mgr;g/lens, except for alphafilcon A and lotrafilcon A, which released a statistically different amount of drug when compared with the other lens materials. Alphafilcon A released 65 ± 1.3 &mgr;g/lens, whereas lotrafilcon A slowly released only 11 ± 0.2 &mgr;g/lens. Conclusions Although most of the lenses released enough drug to have anti-inflammatory action, none of the materials released drug for a long enough period of time to be clinically useful as a drug delivery device.

Acetic and Acrylic Acid Molecular Imprinted Model Silicone Hydrogel Materials for Ciprofloxacin-HCl Delivery

Contact lenses, as an alternative drug delivery vehicle for the eye compared to eye drops, are desirable due to potential advantages in dosing regimen, bioavailability and patient tolerance/compliance. The challenge has been to engineer and develop these materials to sustain drug delivery to the eye for a long period of time. In this study, model silicone hydrogel materials were created using a molecular imprinting strategy to deliver the antibiotic ciprofloxacin. Acetic and acrylic acid were used as the functional monomers, to interact with the ciprofloxacin template to efficiently create recognition cavities within the final polymerized material. Synthesized materials were loaded with 9.06 mM, 0.10 mM and 0.025 mM solutions of ciprofloxacin, and the release of ciprofloxacin into an artificial tear solution was monitored over time. The materials were shown to release for periods varying from 3 to 14 days, dependent on the loading solution, functional monomer concentration and functional monomer:template ratio, with materials with greater monomer:template ratio (8:1 and 16:1 imprinted) tending to release for longer periods of time. Materials with a lower monomer:template ratio (4:1 imprinted) tended to release comparatively greater amounts of ciprofloxacin into solution, but the release was somewhat shorter. The total amount of drug released from the imprinted materials was sufficient to reach levels relevant to inhibit the growth of common ocular isolates of bacteria. This work is one of the first to demonstrate the feasibility of molecular imprinting in model silicone hydrogel-type materials.

Delivery of ketotifen fumarate by commercial contact lens materials.

Purpose. To investigate the uptake and delivery of the anti-allergy drug ketotifen fumarate (KF) by commercially available contact lenses. Methods. A total of 14 different commercially available contact lenses were investigated, including five frequent-replacement silicone hydrogels, three conventional hydrogels, and six daily disposable lenses. Lenses were soaked in a 0.025% KF loading solution for 24 h, and the concentration of KF in solution over time was determined by ultraviolet absorbance at 297 nm. After the 24-h loading period, lenses were placed in fresh vials containing borate buffered saline, and the release of drug into solution at 34°C was monitored for 24 h. Results. All the lenses studied demonstrated significant uptake and release of KF into the borate buffered saline (p < 0.05 compared with initial time point). Lenses with charged surfaces [balafilcon A, etafilcon A, and etafilcon A (daily disposable)] demonstrated the greatest uptake and release of KF. Etafilcon A released 284.5 ± 29.8 &mgr;g/lens, whereas balafilcon A released 227.6 ± 14.7 &mgr;g/lens, which was substantially more (p < 0.05) than the lowest releasing lenses [nelfilcon A (40.4 ± 4.1 &mgr;g/lens) and comfilcon A (110.4 ± 8.9 &mgr;g/lens)]. The majority of lenses were able to match or exceed the total amount of KF commonly administered to the eye using twice-daily dosing of commercially available (0.025%) eye drop formulations. Most of the lenses surveyed reached a plateau concentration of KF relatively quickly, and no lens was able to release KF for longer than 4 h. Conclusions. Commercially available lenses demonstrated the ability to release a clinically relevant amount of KF compared with conventional eye drops. The use of commercially available contact lenses as a KF delivery system in a daily wear scenario may be feasible.

In Vitro and In Vivo Evaluation of Novel Ciprofloxacin-Releasing Silicone Hydrogel Contact Lenses

PURPOSE The purpose of this study was to evaluate ciprofloxacin-releasing silicone hydrogel contact lens materials in vitro and in vivo for the treatment of microbial keratitis. METHODS Model silicone hydrogel contact lens materials were manufactured using a molecular imprinting technique to modify ciprofloxacin release kinetics. Various contact lens properties, including light transmission and surface wettability, were determined, and the in vitro ciprofloxacin release kinetics elucidated using fluorescence spectrophotometry. The materials then were evaluated for their ability to inhibit Pseudomonas aeruginosa growth in vitro and in an in vivo rabbit model of microbial keratitis. RESULTS Synthesized lenses had similar material properties to commercial contact lens materials. There was a decrease in light transmission in the shorter wavelengths due to incorporation of the antibiotic, but over 80% light transmission between 400 and 700 nm. Modified materials released for more than 8 hours, significantly longer than unmodified controls (P < 0.05). In vivo, there was no statistically significant difference between the number of colony-forming units (CFU) recovered from corneas treated with eye drops and those treated with one of two modified contact lenses (P > 0.05), which is significantly less than corneas treated with unmodified control lenses or those that received no treatment at all (P < 0.05). CONCLUSIONS These novel contact lenses designed for the extended release of ciprofloxacin may be beneficial to supplement or augment future treatments of sight-threatening microbial keratitis.

Release of Ciprofloxacin-HCl and Dexamethasone Phosphate by Hyaluronic Acid Containing Silicone Polymers

The purpose of this study was to determine the effect of the covalent incorporation of hyaluronic acid (HA) into conventional hydrogel and hydrogels containing silicone as models for contact lens materials on the uptake and release of the fluoroquinolone antibiotic ciprofloxacin and the anti-inflammatory steroid dexamethasone phosphate. A 3 mg/mL ciprofloxacin solution (0.3% w/v) and a 1 mg/mL dexamethasone phosphate solution (0.1%) was prepared in borate buffered saline. Three hydrogel material samples (pHEMA; pHEMA TRIS; DMAA TRIS) were prepared with and without the covalent incorporation of HA of molecular weight (MW) 35 or 132 kDa. Hydrogel discs were punched from a sheet of material with a uniform diameter of 5 mm. Uptake kinetics were evaluated at room temperature by soaking the discs for 24 h. Release kinetics were evaluated by placing the drug-loaded discs in saline at 34 °C in a shaking water bath. At various time points over 6–7 days, aliquots of the release medium were assayed for drug amounts. The majority of the materials tested released sufficient drug to be clinically relevant in an ophthalmic application, reaching desired concentrations for antibiotic or anti-inflammatory activity in solution. Overall, the silicone-based hydrogels (pHEMA TRIS and DMAA TRIS), released lower amounts of drug than the conventional pHEMA material (p < 0.001). Materials with HA MW132 released more ciprofloxacin compared to materials with HA MW35 and lenses without HA (p < 0.02). Some HA-based materials were still releasing the drug after 6 days.

In Vivo Studies Evaluating the Use of Contact Lenses for Drug Delivery.

ABSTRACT This review highlights the current state of knowledge of in vivo testing of drug-delivering contact lenses. There has been a significant increase in interest in alternative means to deliver ocular pharmaceuticals, and within the past few decades, contact lenses have emerged as a vehicle of interest because of their biocompatibility and acceptance by both eye care professionals and the public. Using techniques such as molecular imprinting, vitamin E diffusion barriers, ionic reservoirs, and drug-impregnated films, significantly improved drug release kinetics have been observed in vitro. Extension of these results into in vivo studies has thus far been limited but has led to evidence of the viability of this drug delivery platform by demonstrating improved drug residence time, drug penetration, and clinical outcomes when compared with conventional therapy such as eye drops. The evidence supporting these improvements has occurred in both animal models and small human trials and is presented within this review.

Insights to Using Contact Lenses for Drug Delivery

There has been considerable interest in the potential application of contact lenses for ocular drug delivery. This short communication provides an overview of the challenges faced by delivering drugs using contact lenses, highlights the solutions to limitations that have already been achieved, and describes the barriers that remain before commercial application can be realized.

Contact lenses for ophthalmic drug delivery

Contact lenses as a means to deliver pharmaceuticals to the eye have seen a significant increase in research interest in the past few years. This review will detail the in vitro experiments which have investigated use of these contact lenses in the context of the desired pharmacological treatment goals in the management of infectious, inflammatory, allergic and glaucomatous diseases of the eye. The techniques researchers have employed to modify and tailor drug release rates from these materials, including the use of vitamin E diffusion barriers, modified ionicity, molecular imprinting and incorporation of drug reservoirs, will be discussed, as well as their impact on drug release kinetics. Finally, the demonstration of the feasibility of these materials when applied in vivo in animal models as well as in humans with and without disease will be presented and their results discussed relating to their implications for the future of the field.Contact lenses as a means to deliver pharmaceuticals to the eye have seen a significant increase in research interest in the past few years. This review will detail the in vitro experiments which have investigated use of these contact lenses in the context of the desired pharmacological treatment goals in the management of infectious, inflammatory, allergic and glaucomatous diseases of the eye. The techniques researchers have employed to modify and tailor drug release rates from these materials, including the use of vitamin E diffusion barriers, modified ionicity, molecular imprinting and incorporation of drug reservoirs, will be discussed, as well as their impact on drug release kinetics. Finally, the demonstration of the feasibility of these materials when applied in vivo in animal models as well as in humans with and without disease will be presented and their results discussed relating to their implications for the future of the field.

In vitro release of two anti-muscarinic drugs from soft contact lenses

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.