Article

# Studies on the uptake and release of fluoroquinolones by disposable contact lenses

Authors:
If you want to read the PDF, try requesting it from the authors.

## Abstract

To evaluate the ability of three types of disposable contact lenses to take up and release three kinds of fluoroquinolones in vitro. We evaluated three FDA-approved disposable soft contact lenses (1-Day Acuvue, Medalist, and 14UV) for their ability to absorb and release three kinds of fluoroquinolones. Contact lenses were presoaked in fluoroquinolones for 1, 4, and 24 hours, and the uptake was determined by measuring the concentration of fluoroquinolones in the three types of disposable soft contact lenses by high pressure liquid chromatography (HPLC). After uptake, the lenses were placed in fresh saline baths, and release rates from the lenses were determined by measuring the concentration of fluoroquinolones in the saline baths by HPLC. The disposable soft contact lens with the highest uptake of fluoroquinolones was the 1-Day Acuvue. After presoaking, drug concentrations in the 1-Day Acuvue and Medalist were higher than their theoretical saturation concentrations (i.e., the concentration of the fluoroquinolone eye drops [0.3%]). The release rates from the 1-Day Acuvue and Medalist lenses were slower than for the 14 UV lens. These results indicate that among the lenses tested, the most practical drug delivery system is the 1-Day Acuvue disposable soft contact lens.

## No full-text available

... Over the last decade, there has been considerable interest in using contact lenses (CLs) beyond their intended application in vision correction. 1 One area of research that is rapidly gaining traction is ocular drug delivery using CLs. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Drug delivery using CLs was conceptualized to address the key problems associated with conventional therapies to treat eye diseases such as glaucoma, 16 infection, 6,10,15 myopia, 17 allergies, 8 and dry eye. 18,19 Currently, eye drops and ointments account for over 90% of all ophthalmic formulations for ocular drug delivery. ...
... So while there are numerous studies on CL drug delivery, far fewer have reported data on drug uptake. [2][3][4][5][6][7][8][9][10][11][12][13][14]31,32 These studies typically quantify drug uptake into the lens by measuring the concentration of the drugloading solution at the beginning and the end of the incubation period. [2][3][4][5][6][7][8][9][10][11][12][13]31,32 The difference in drug concentration is then attributed to the amount of drugs sorbed by the lens. ...
... [2][3][4][5][6][7][8][9][10][11][12][13][14]31,32 These studies typically quantify drug uptake into the lens by measuring the concentration of the drugloading solution at the beginning and the end of the incubation period. [2][3][4][5][6][7][8][9][10][11][12][13]31,32 The difference in drug concentration is then attributed to the amount of drugs sorbed by the lens. [2][3][4][5][6][7][8][9][10][11][12][13]31,32 However, there are some inherent problems with this indirect measurement approach. ...
Article
Full-text available
Purpose: To develop a simple extraction procedure to quantify the uptake of four topical ocular pharmaceutical drugs into contact lenses (CLs). Methods: Four silicone hydrogel (SH) CLs (balafilcon A, senofilcon A, lotrafilcon B, comfilcon B) and four conventional hydrogel (CH) CLs (nesofilcon A, hilafilcon B, nelfilcon A, etafilcon A) were evaluated. The drugs studied were natamycin, moxifloxacin, timolol maleate, and ketotifen fumarate. For drug incubation, three CLs of each type were placed in 1 mL of 1 mg/mL drug-loading solution for 24 hours. The lenses were then extracted in 2 mL methanol for 2 hours. This process was repeated to obtain a total of three extraction cycles. Detection of natamycin, moxifloxacin, ketotifen fumarate, and timolol maleate were measured by absorbance at 305, 287, 297, and 295 nm, respectively. Results: The majority of the drugs were extracted after the first extraction cycle (P< 0.001). For moxifloxacin and timolol, CH CLs had higher drug uptake than SH CLs (P< 0.05). There were no differences in drug uptake between CH CLs and SH CLs for natamycin and ketotifen (P> 0.05). Conclusions: This study provides a simple approach to determine drug uptake into CLs. This method can also be modified, such as changing the extraction time, extraction cycles, or extraction solvent to better suit other drugs and CL combinations. Translational relevance: There is considerable interest in using CLs for ocular drug delivery. Accurately quantifying drug uptake on CLs has been a challenge. Hence, this study provides a simple method to quantify drug uptake in CLs.
... In fixed volume release studies, parameters such as the release medium and its volume, as well as mixing condition, are critically important [11]. The amount of released drug and the elution time have been shown to be consistently smaller when tested using the in vitro fixed volume model compared to in vivo experiments [12,14,[18][19][20][21][22][23]. In the fixed volume conditions, the drug release mechanism is governed by diffusion, where concentration gradients generate the driving force and the ratio of the concentration between the contact lens and the medium is dictated by the partition ratio. ...
... Due to the lack of previous in vitro studies on prostaglandin analogues, our results can only be compared to the release of drugs from the contact lens materials with similar size and hydrophobicity. Previous in vivo studies have shown a prolonged release of relatively hydrophobic drugs such as ketotifen [21] and lomefloxacin [23], however such release profiles could not be replicated in vitro using a fixed volume release model [12,22]. The extended release of latanoprost observed in the monolayer and multilayer in vitro models correlates well with the extended release profiles of the hydrophobic drugs observed in vivo [21,23]. ...
... Previous in vivo studies have shown a prolonged release of relatively hydrophobic drugs such as ketotifen [21] and lomefloxacin [23], however such release profiles could not be replicated in vitro using a fixed volume release model [12,22]. The extended release of latanoprost observed in the monolayer and multilayer in vitro models correlates well with the extended release profiles of the hydrophobic drugs observed in vivo [21,23]. The release results of latanoprost in the no-cells model is also comparable to the release results of hydrophobic compounds in fixed volume solution [12,22]. ...
Article
Full-text available
In this study, we compared, for the first time, the release of a 432 kDa prostaglandin [Formula: see text] analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ([Formula: see text] solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6 [Formula: see text] of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 [Formula: see text], was released, ([Formula: see text]). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.
... Besides, the physicochemical properties of the drug used affects both release and uptake efficiencies [45]. The use of preformed contact lenses in drug loading and release has been investigated in several studies [45][46][47][48][49][50] and summarized in Table 4. ...
... Tian et al. investigated the use of 1-day disposable soft contact lens (SCL) on the delivery of lomefloxacin across albino rabbits' eye. Despite achieving higher drug levels in the cornea and aqueous humor over eye drops, the SCL managed to maintain drug release for only a few hours [47]. Karlgard et al. demonstrated that both p-HEMA and silicone-based contact lenses release the drug within 10 minutes, suggesting a limitation as a sustained-release system. ...
... Fluoroquinolones 1, 4 and 24 h 1-day Acuvue showed highest uptake of fluoroquinolones. 1-day Acuvue, Medalist have slower release compared with 14 UV [47] Acuvue ® Gentamicin, kanamycin, tobramycin, ciprofloxacin or ofloxacin 1 h Released between 190 and 1000 μg of antibiotics, which was lower or in the same order of magnitude as obtained with application of eye drops [48] Lotrafilcon, balafilconetafilcon, alphafilcon, polymacon, vifilcon and omafilcon Cromolyn sodium, ketotifenfumarate, ketorolac tromethamine and dexamethasone ...
Article
Full-text available
Although conventional eye drops comprise over 90% of the marketed ocular dosage forms, they do have limitations, such as poor ocular drug bioavailability and systemic side effects; contact lenses are amongst the new delivery systems and devices that could overcome some of these problems. The most common approach to load drug molecules into contact lenses includes soaking in a drug solution. This approach had some success, but failed to achieve controlled/sustained drug release to the eye. One the other hand, nanoreservoir systems comprising nanoparticles, cyclodextrins, liposomes or surfactant aggregates being incorporated into the contact lenses could offer a plausible solution. This review highlights the status quo with contact lenses as ocular drug-delivery carriers and identifies possible future directions.
... Almost every major class of ophthalmic medications in use has been investigated in vitro for their uptake and release into commercially available contact lenses, from anti-allergy [205,206], antibacterials [207][208][209][210][211][212][213], antifungals [214], anti-inflammatories [206,211,215], antimyopia [216], antiviral [217], anaesthetics [218][219][220][221], dry eye [211,222,223], non-steroidal anti-inflammatory agents [206] and glaucoma agents [224][225][226][227]. The influence of the in vitro testing conditions on drug uptake and release has also been explored across different studies, with the influence of aspects as broad as the concentration of the drug loading solution [228], the rate of replenishment or replacement of the drug release solution [217,222], the composition of the drug release solution (saline versus a synthetic artificial tear analogue) [225,226,227] and mechanical effects of simulated blinking [229]. ...
Article
Contact lenses in the future will likely have functions other than correction of refractive error. Lenses designed to control the development of myopia are already commercially available. Contact lenses as drug delivery devices and powered through advancements in nanotechnology will open up further opportunities for unique uses of contact lenses. This review examines the use, or potential use, of contact lenses aside from their role to correct refractive error. Contact lenses can be used to detect systemic and ocular surface diseases, treat and manage various ocular conditions and as devices that can correct presbyopia, control the development of myopia or be used for augmented vision. There is also discussion of new developments in contact lens packaging and storage cases. The use of contact lenses as devices to detect systemic disease has mostly focussed on detecting changes to glucose levels in tears for monitoring diabetic control. Glucose can be detected using changes in colour, fluorescence or generation of electric signals by embedded sensors such as boronic acid, concanavalin A or glucose oxidase. Contact lenses that have gained regulatory approval can measure changes in intraocular pressure to monitor glaucoma by measuring small changes in corneal shape. Challenges include integrating sensors into contact lenses and detecting the signals generated. Various techniques are used to optimise uptake and release of the drugs to the ocular surface to treat diseases such as dry eye, glaucoma, infection and allergy. Contact lenses that either mechanically or electronically change their shape are being investigated for the management of presbyopia. Contact lenses that slow the development of myopia are based upon incorporating concentric rings of plus power, peripheral optical zone(s) with add power or non-monotonic variations in power. Various forms of these lenses have shown a reduction in myopia in clinical trials and are available in various markets.
... Polymacon and alphafilcon A lenses (see Table I for lens composition) saturated with ciprofloxacin by immersion in a commercial eye-drop solution for one hour led to remarkably greater drug levels in both cornea (8.03 and 6.43 μg, respectively) and aqueous humor (0.361 and 0.240 μg, respectively) than the direct application of the eye drops (0.45 μg in cornea and 0.007 μg in aqueous humor) [60,61]. Etafilcon A (1-Day Acuvue) lenses, when loaded by immersion in eye-drop solutions, provided higher concentrations of antifungals, aminoglycosides and fluoroquinolones in aqueous humor than when Table I the eye drops were directly instilled [62][63][64]. In a study conducted on patients who required cataract extraction, all of whom preoperatively wore ofloxacin-loaded lenses for 4-5 h and 92 % of whom wore ciprofloxacin-loaded lenses, they had aqueous humor concentrations above the MIC 90 of Staphylococcus epidermidis at the beginning of the surgery [64]. ...
Article
Soft contact lenses (SCLs) are particularly attractive as drug delivery devices capable of overcoming certain limitations of conventional ophthalmic formulations. Although the main use of commercially-available SCLs is for correcting ametropia problems, they may also uptake certain drugs and release them into the postlens lachrymal fluid, minimizing the clearance and the sorption through the conjunctiva. Novel approaches to enhance the capability of SCLs to load drugs and control release may make these optical devices behave as advanced drug delivery systems, fulfilling the requirements of both chronic and acute ocular diseases. Among those approaches, the application of the molecular imprinting technology during SCL manufacture enables the creation in the lens structure of imprinted pockets that memorize the spatial features and bonding preferences of the drug and provide the lens with a high affinity for a given drug. Imprinted SCLs could prolong the permanence of the drug in the precorneal area and provide sustained drug levels, increasing ocular bioavailability and avoiding systemic side-effects. In this review, the potential and the advantages/drawbacks of drug-imprinted SCLs are critically analyzed and examples of the application of the molecular imprinting technology to β-adrenergic antagonist, antimicrobials, antihistamines and ocular comfort ingredients are shown.
... For example, polymacon and alphafilcon A lenses loaded with ciprofloxacin by soaking for 1 hour in commercial eye drop solution led to remarkably greater drug levels in both corneal tissue and aqueous humour at 6 h after application, compared with the direct application of eye drops (polymacon: 8.034 µg; alphafilcon: 6.432 µg, eye drops: 0.451 µg in cornea; polymacon: 0.361 µg; alphafilcon: 0.240 µg, eye drops: 0.0071 µg in aqueous humour) [207,208]. Similarly, etafilcon A (1-Day Acuvue ® ) CLs loaded by immersion in eye drop solutions provided higher concentrations of antifungals, aminoglycosides and fluoroquinolones in aqueous humour than when the eye drops were directly instilled [56][57][58]. Wearing of ofloxacin-loaded or ciprofloxacin-loaded lenses for 4-5 h before cataract extraction resulted in aqueous humour concentrations above the MIC 90 of Staphylococcus epidermidis at the beginning of surgery [58]. Nevertheless, there are many drugs (chloramphenicol, epinephrine and pilocarpine) future science group that do not show affinity for pHEMA lenses, and in those cases the soaked lenses hardly led to one tenth of the aqueous humour concentration that can be achieved using eye drops [59][60][61]. ...
Article
Full-text available
The use of contact lenses as ocular bandages for drug delivery was envisioned nearly 50 years ago by Wichterle and co-workers. Despite the therapeutic advantages that can be obtained, this application has to face up to the poor affinity shown by commercially available contact lenses for most ophthalmic drugs, resulting in small amounts of drug being loaded and short time of therapeutic levels in the eye structures. Novel strategies that appeared in the beginning of 21st century, for example coating lenses with vitamin E, incorporation of drug nanocarriers or application of molecular imprinting technology, are becoming relevant tools for development of true drug/contact lens combination products that may be available for ocular therapy in the foreseeable future.
... The major problem with commercial contact lenses is that most of the drug diffuses from these systems within a few hours [44]. Drugs like cromolyn sodium, ketotifen fumarate, ketorolac tromethamine, dexamethasone sodium phosphate [45], timolol [46], pilocarpine [47], and fluoroquinolones [48] have been studied for uptake and release by soft contact lenses. None of these drugs seem to release drugs for more than 6 h. ...
... For example, polymacon and alphafilcon A lenses loaded with ciprofloxacin by soaking for 1 hour in commercial eye drop solution led to remarkably greater drug levels in both corneal tissue and aqueous humour at 6 h after application, compared with the direct application of eye drops (polymacon: 8.034 µg; alphafilcon: 6.432 µg, eye drops: 0.451 µg in cornea; polymacon: 0.361 µg; alphafilcon: 0.240 µg, eye drops: 0.0071 µg in aqueous humour) [207,208]. Similarly, etafilcon A (1-Day Acuvue ® ) CLs loaded by immersion in eye drop solutions provided higher concentrations of antifungals, aminoglycosides and fluoroquinolones in aqueous humour than when the eye drops were directly instilled [56][57][58]. Wearing of ofloxacin-loaded or ciprofloxacin-loaded lenses for 4-5 h before cataract extraction resulted in aqueous humour concentrations above the MIC 90 of Staphylococcus epidermidis at the beginning of surgery [58]. Nevertheless, there are many drugs (chloramphenicol, epinephrine and pilocarpine) future science group that do not show affinity for pHEMA lenses, and in those cases the soaked lenses hardly led to one tenth of the aqueous humour concentration that can be achieved using eye drops [59][60][61]. ...
Article
Currently, approximately 100 million people are estimated to be wearing contact lenses, and the number is increasing exponentially. Although the main use of contact lenses is for correcting ametropia problems, they also hold interest as therapeutic devices for the relief of ocular pain, promotion of corneal healing, mechanical protection and support, maintenance of corneal epithelial hydration, and drug delivery. Ocular drug administration is particularly challenging and recent research has been directed towards the design of novel drug delivery systems capable of prolonging the permanence of the drug in the precorneal area and, thus, potentially increasing bioavailability and minimizing adverse effects. Conventional hydrogel soft contact lenses have the ability to absorb some drugs and release them into the post-lens lacrimal fluid, minimizing clearance and sorption through the conjunctiva. Their ability to be a drug reservoir strongly depends on the water content and thickness of the lens, the molecular weight of the drug, the concentration of the drug loading solution and the time the lens remains in it. However, the ability of contact lenses to load drugs and to control their release is in general inadequate and the following approaches, based on modifications of the polymer network, are currently under evaluation: (i) covalent binding of the drug to the lens network via labile bonds; (ii) inclusion of the drug in colloidal structures that are dispersed in the lens and are responsible for controlling drug release; (iii) functionalization of the network with chemical groups that work as ion-exchange resins; and (iv) creation in the lens structure of imprinted pockets that memorize the spatial features and bonding preferences of the drug and provide the lens with a high affinity and selectivity for a given drug. In this review, the possibilities and the advantages/drawbacks of these new types of contact lenses as drug delivery systems are critically analyzed.
... There were soaked in fluoroquinolone solutions during different times. In conclusion, the higher uptake of drug was for the 1-Day Acuvue ® lens and the release rates were slower for the 1-Day and the Medallist ® than for the 14UV, but the most practicable system was the 1-Day Acuvue ® [107]. These conclusions were previously exposed by Hehl et al. [108]. ...
Article
Full-text available
The last fifty years, ophthalmic drug delivery research has made much progress, challenging scientists about the advantages and limitations of this drug delivery approach. Topical eye drops are the most commonly used formulation in ocular drug delivery. Despite the good tolerance for patients, this topical administration is only focus on the anterior ocular diseases and had a high precorneal loss of drugs due to the tears production and ocular barriers. Antibiotics are popularly used in solution or in ointment for the ophthalmic route. However, their local bioavailability needs to be improved in order to decrease the frequency of administrations and the side effects and to increase their therapeutic efficiency. For this purpose, sustained release forms for ophthalmic delivery of antibiotics were developed. This review briefly describes the ocular administration with the ocular barriers and the currently topical forms. It focuses on experimental results to bypass the limitations of ocular antibiotic delivery with new ocular technology as colloidal and in situ gelling systems or with the improvement of existing forms as implants and contact lenses. Nanotechnology is presently a promising drug delivery way to provide protection of antibiotics and improve pathway through ocular barriers and deliver drugs to specific target sites.
... Since 1960, contact lenses and shields have been investigated to deliver drugs to the eye (Dixon et al., 2015;Jessen, 1964;Tian et al., 2001aTian et al., , 2001bWichterle and Lim, 1960;Willoughby et al., 2002). Most of them were made by simply dipping the material (often a hydrogel) into a drug solution (Schultz and Morck, 2010). ...
Article
Contact lens solutions are highly complex mixtures of biocides (preservatives), surfactants, and other agents designed to disinfect, clean, and wet contact lenses. The commercialization of silicone hydrogel (SiHy) lenses has resulted in unique challenges to the manufacturers of contact lens solutions, because the properties of these materials differ markedly from those seen previously with poly-hydroxyethyl methacrylate-based hydrogels. Historically, hydrogel lens uptake and release of low-molecular weight preservatives such as chlorhexidine and thimerosal were known to result in allergic reactions, resulting in corneal irritation, stinging, conjunctival hyperemia, development of corneal infiltrates, palpebral lid changes, and corneal staining. However, little is known about the interaction of modern care systems with modern soft lens materials. Factors to be considered when evaluating the uptake and release of care components include the water content, charge, relative hydrophobicity, surface treatment, and porosity of the lens material, in conjunction with the concentration, charge/molecule, ionicity in the product matrix, molecular weight, and hydrophobicity of the care component in question. These factors control the sorption of the solution components by lenses, resulting in a variety of differences in the amount of the component taken up into the lens material and the amount and rate of subsequent release onto the ocular surface. Because both natural (ocular) and environmental biota become part of the solution-lens system during regimen use of any lens care product, these extraneously introduced substances should also be considered regarding their potential for uptake and either subsequent release onto the ocular surface or functioning as a scaffold for the adhesion of microbes. This article will review current knowledge concerning these interactions and investigate what clinically observable complications may arise from these interactions. It also reviews whether current methods to determine these interactions could be improved on.
Article
To investigate the uptake and release kinetics of the synthetic glucocorticoid anti-inflammatory drug dexamethasone into various conventional and silicone hydrogel contact lens materials. 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. 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 microg/lens and 102 +/- 11 microg/lens, respectively, and galyfilcon took up the least amount of drug at 34 +/- 6 microg/lens. The release of the drug from the lens materials was also statistically significant. The majority of the lenses released between 20 and 30 microg/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 microg/lens, whereas lotrafilcon A slowly released only 11 +/- 0.2 microg/lens. 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.
Article
Eye drops are inefficient means of delivering ophthalmic drugs because of limited bioavailability and these can cause significant side effects due to systemic uptake of the drug. The bioavailability for ophthalmic drugs can be increased significantly by using contact lenses. This study focuses on the development of surfactant-laden poly-hydroxy ethyl methacrylate (p-HEMA) contact lenses that can release Cyclosporine A (CyA) at a controlled rate for extended periods of time. We focus on various Brij surfactants to investigate the effects of chain length and the presence of an unsaturated group on the drug release dynamics and partitioning inside the surfactant domains inside the gel. The gels were imaged by cryogenic scanning electron microscopy (cryo-SEM) to obtain direct evidence of the presence of surfactant aggregates in the gel, and to investigate the detailed microstructure for different surfactants. The images show a distribution of nano pores inside the surfactant-laden hydrogels which we speculate are regions of surfactant aggregates, possibly vesicles that have a high affinity for the hydrophobic drug molecule. The gels are further characterized by studying their mechanical and physical properties such as transparency, surface contact angle and equilibrium water content to determine their suitability as extended wear contact lenses. Results show that Brij surfactant-laden p-HEMA gels provide extended release of CyA, and possess suitable mechanical and optical properties for contact lens applications. The gels are not as effective for extended release of two other hydrophobic ophthalmic drugs, dexamethasone (DMS) and dexamethasone 21 acetate (DMSA) because of insufficient partitioning inside the surfactant aggregates.
Article
Currently, the armamentarium of contact lenses that can be used for therapeutic effect provides a wider selection of lenses than ever before. If the therapeutic goal is protection and healing of the corneal epithelium, epithelial or stromal edema is best avoided, and the selection of a high-Dk silicone hydrogel (balafilcon A, lotrafilcon A) lens or a very thin membrane-type lens (crofilcon) is the best choice. If the goal is surface protection as well as stimulation of stromal wound vascularization, selection of a low-water content, thick, hydrophilic lens is the better option. If the patient is prone to lens loss or requires frequent replacement of the therapeutic lens, a prudent economic decision is to select a daily disposable moderate-water content lens. Specific circumstances may mandate the selection of a specific therapeutic lens. Patients with a prior history of active giant papillary conjunctivitis may be better served by the use of a crofilcon glyceryl methacrylate lens, which has a lower incidence of this complication. Patients who have dry eye may benefit from a higher-water content lens if adequate unpreserved tear supplementation is provided with or without punctal occlusion. The options when selecting a therapeutic contact lens are wider than ever before. Although the new generation of high-Dk lenses promises fewer limiting problems of vascularization and infection, one can use the older traditional therapeutic lenses when induced vascularization of the cornea is needed or when an economic necessity exists. Not all of the available lenses are FDA approved for therapeutic use, and such wear is an off-label use. The patient should be informed of the goal of therapy as well as the benefits and risks of therapeutic contact lenses.
Article
The purpose of this work was to report the findings of a survey of current modes of bandage lens (BL) use by optometrists and ophthalmologists in Canada and the United States in 2002. Two thousand voluntary surveys were sent to ophthalmic practitioners across the United States and Canada. The survey contained a questionnaire with 15 questions about the practitioner's background and BL-prescribing trends and views. It also contained a 10-patient list with parameters such as patient profile, BL type, and pharmaceutical use. Seventy-two percent of those opthalmic practitioners who returned surveys have prescribed soft contact lenses for therapeutic purposes. BLs are most often used for corneal wound healing and for managing postoperative complications. Pharmaceuticals are concomitantly administered in more than 81% of the patients treated with BLs. The most commonly prescribed pharmaceuticals are antibiotics (47.5% of patients) and antiinflammatory drugs (42% of patients). ACUVUE and Focus Night & Day lenses are the most popular choices for BLs. Most respondents (93%), regardless of whether they routinely prescribed BLs, would be interested in a BL that could deliver a topical pharmaceutical drug. The results from the survey indicated that BL use is prevalent across North America. The BL-prescribing habits of North American practitioners indicate that there is a strong interest and need for a drug-delivering therapeutic soft contact lens.
Article
Isothermal titration calorimetry (ITC) was used to identify the optimal timolol:functional monomer ratio for preparing soft contact lenses (SCLs) able to sustain drug release. ITC profiles revealed that each timolol molecule required six to eight acrylic acid (AAc) monomers to saturate the binding and that these ratios could be the most suitable for creating imprinted cavities. Various poly(hydroxyethyl methacrylate-co-AAc) hydrogels 0.2 and 0.9 mm thick were prepared with timolol:AAc molar ratios ranging from 1 : 6 to 1 : 32 and also in the absence of timolol. The hydrogels were reloaded with timolol by immersion in 0.04, 0.06, 0.08, and 0.10 mM drug solutions. Both imprinted and nonimprinted hydrogels showed a high affinity for the drug because of the presence of AAc. Nevertheless, the 1 : 6 and 1 : 8 imprinted hydrogels loaded less timolol but sustained the release better than the other hydrogels. These differences were explained in terms of the different arrangement of the functional monomers along the network. The imprinting effect was more noticeable in the case of the thinnest hydrogels, where the contribution of the diffusion path to the release rate was smaller. The results obtained prove the interest of ITC for the rational design of drug-imprinted networks to be used as medicated SCLs. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Article
Conventionally, antimicrobial drugs developed and approved for systemic infections are re-investigated for ocular infections. However, developing a new antimicrobial agent with good intraocular penetration by considering the anatomical and physiological constraints exerted by the barriers of eye is not a popularly perceived strategy. For the last three to four decades much emphasis has been placed on drug delivery systems to enhance the ocular penetration of antimicrobial agents. In order to compare ocular drug delivery strategies for ocular infections, the existing studies and methods were revisited using an extensive literature search. The present analysis also encompasses the scientific outcomes of endophthalmitis studies to interpret the intraocular penetration data of various antimicrobial agents and their requirements before and after the onset of inflammation. This article critically analyses the systemic and topical drug delivery methods adopted for antimicrobial use and their applicability to the newer class of antimicrobial agents, thus giving space for further developments. This review emphasizes the requirement of stage-by-stage insights about ocular infections, the need for an eye-specific antimicrobial agent and the inevitability of an appropriate drug delivery approach to revolutionize future therapy.
Article
Full-text available
Article
Purpose: The purpose of this study was to investigate the uptake and the release of antibiotics from a newly synthesized drug delivery hydrogel soft contact lens (SCL) using an ion ligand mechanism. Methods: The antibiotics used were Gatifloxacin (GFLX) and Moxifloxacin (MFLX). The uptake amount and the sustained-release kinetics of antibiotics were investigated in vitro, and were also compared with newly synthesized SCLs, etafilcon A and polymacon. The antibiotic concentrations in the cornea, aqueous humor, and crystalline lens, and the effect against bacterial proliferation were investigated in vivo using rabbit subjects. Additionally the drug release efficacy of the new SCL was compared with that of eye drop administrations. Results: In vitro, antibiotic uptake was increased with the weight percent (wt%) of the anionic group, and the released amount of antibiotics was highest during the initial 1 hour period, which then decreased over the next 72 hours. The released antibiotics volume of the new SCLs was significantly higher throughout 72 hours than that of the other two materials, etafilcon A and polymacon (P < 0.01). Whereas in vivo, the concentrations found in the cornea and aqueous humor were higher than those for the eye drop groups (P < 0.05 or P < 0.01). Antibiotic release at those sites decreased over 72 hours. No bacterial populations were detectable in the group treated with the new SCL presoaked in antibiotics throughout the experimental periods. Conclusions: The new SCLs released the antibiotics over several days, and showed improved penetration into the eye, along with prevention of bacterial proliferation.
Article
Objectives: To determine the equilibrium binding constant (EB) values of bimatoprost and tafluprost drug product formulations in contact with lotrafilcon A soft contact lenses and to characterize the importance of drug molecule hydrophobicity in controlling the binding interactions. Methods: Bimatoprost Ophthalmic Solution and Tafluprost Ophthalmic Solution (Saflutan) were incubated with lotrafilcon A lens material for timed intervals at 25°C and 37°C. Aliquots were withdrawn, filtered, and tested using reverse-phase ultrahigh-performance liquid chromatography with respect to [bimatoprost] or [tafluprost] remaining in the solution. A series of homologous dialkyl phthalate esters and a series of homologous p-hydroxybenzoic acid alkyl esters were also tested as reference compounds. Results: Bimatoprost and tafluprost were rapidly (within 15 min) absorbed from the solution by lotrafilcon A lenses, reaching an equilibrium within 60 min. At any lens:solution (w/v) ratio, the extent of drug binding to lens material was greater for tafluprost than for bimatoprost. The log(EB) values correlated with solute octanol:water partition coefficient (logP) values, indicating that hydrophobic interactions are important in controlling solute partitioning into the lens material. Conclusions: This study established the quantitative relationships between tafluprost and bimatoprost binding to lotrafilcon A lenses. The fraction of bimatoprost or tafluprost that binds to lotrafilcon A increases with increasing lens:solution (w/v) ratio. For a 60 µL dose volume applied to a single contact lens, 16% of initially present bimatoprost remains in the solution, whereas only 6% of initially present tafluprost remains in the solution. These calculations clearly demonstrate that both drugs partition extensively into lotrafilcon A contact lens material. Although the clinical implications of such binding can only be surmised, it would seem prudent to caution contact lens wearers to remove the lenses before administering either prostaglandin drug.
Article
Silver in various forms has long been recognized for antimicrobial properties, both in biomedical devices and in eyes. However, soluble drugs used on the ocular surface are rapidly cleared through tear ducts and eventually ingested, resulting in decreased efficacy of the drug on its target tissue and potential concern for systemic side effects. Silver nanoparticles were studied as a source of anti-microbial silver for possible controlled-release contact lens controlled delivery formulations. Silver ion release over a period of several weeks from nanoparticle sources of various sizes and doses was evaluated in vitro against Pseudomonas aeruginosa strain PAO1. Mammalian cell viability and cytokine expression in response to silver nanoparticle exposure is evaluated using corneal epithelial cells and eye-associated macrophages cultured in vitro in serum-free media. Minimal microcidal and cell toxic effects were observed for several silver nanoparticle suspensions and aqueous extraction times for bulk total silver concentrations commensurate with comparative silver ion (e.g., $${\text{Ag}}_{\left( {{\text{aq}}} \right)}^ +$$) toxicity. This indicates that (1) silver particles themselves in these size ranges (20–60 nm diameter) are not microcidal under conditions tested, and (2) insufficient silver ion is generated from these particles at these silver ion-equivalent loadings to produce observable biological effects compared to silver ions in these in vitro assays. This is consistent with confounding literature describing both efficacy and lack of microcidal effects for silver nanoparticles, depending on milieu, surface oxide properties, and size. If dosing allows substantially increased silver particle loading in the lens to produce sufficient pathogen-toxic silver ions and/or particle-microbe direct contact, the bactericidal efficacy of silver nanoparticles in vitro could possibly limit bacterial colonization problems associated with extended-wear contact lenses.
Article
Soft contact lenses have generated growing interest for ocular drug delivery due to the potential offered for enhanced drug bioavailability in ocular tissues. Commercially available soft contact lenses offer several advantages for ocular drug delivery as they are manufactured on a large scale, which guarantees the availability of a consistent and reproducible product, and their favorable safety profile is well-established through broad clinical use. Here we critically review the rationale for using commercially available soft contact lenses for ocular drug delivery; summarize the evolution of materials used in lens fabrication; and explore various methods used to improve the drug release characteristics and its tissue uptake. While significant progress has been made, several issues still require further attention for commercial launch of a viable drug release contact lens product, including control of initial burst release, shelf-life stability, and drug loss during processing or storage.
Article
This review covers the progress within the field of drug releasing contact lenses since 1965. It highlights the enormous potential of controlled release mechanisms and offers a comprehensive, comparative review of lenses, drugs, methods, drug loading, drug delivery rate, and release duration. Methods have included molecular imprinting as well various forms of mediated release via carriers, surfactants, inclusion complexes, and molecular barriers. Drug-soaked lens were the earliest releasing lenses, but they offer very little control over the release profile with low drug loading, are characterized by decaying, Fickian release rates, and typically reach completion in a very short amount of time. Molecular imprinting is consistently one of the most promising and versatile methods of enhanced drug loading and extended release with tailorable control over release rate when factors are balanced such as lens thickness, material, and release media and conditions.
Research
Full-text available
review article :Development of ocular drug delivery systems using molecularly imprinted soft contact lenses
Research
Full-text available
review article: Development of ocular drug delivery systems using molecularly imprinted soft contact lenses
Article
Full-text available
In this research we compare the efficiency of noninvasive intraocular-delivering methods of different dosage forms of levofloxacin (LF) with the help of soft contact lens (SCL) and eye drops of LF and LF with the presence of prolongator — hypromellose. It is revealed, that SCL saturated with levofloxacin achieve therapeutic concentration in aqueous humor. This is due to the gradual release of antibiotic from the SCL in the anterior chamber. Installations of eye drops of LF and LF with hypromellose achieve minimum inhibitory concentration of fluoroquinolone in aqueous humor during 3 and 5 hours respectively. It is discussed the using of each dosage form in preventive and therapeutic purposes.
Article
: 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.
Article
Cyclosporine A (CyA) is an immunosuppressant drug that is used for treating a variety of ocular diseases and disorders. CyA is commonly delivered via eye drops, which is highly inefficient due to a low bioavailability of less than 5%. The bioavailability of ophthalmic drugs can be substantially improved to about 50% by delivering them via contact lenses. This paper focuses on the development of nanostructured poly (2-hydroxyethyl methacrylate) (p-HEMA) hydrogels containing microemulsions or micelles of Brij 97 (C(18)H(35)(OCH(2)CH(2))(10)) for extended delivery of CyA. Release of CyA from these nanostructured hydrogels was performed in vitro to explore the mechanisms of release and the effects of surfactant concentration, processing conditions and storage on the release kinetics. Results show that the surfactant and microemulsion-laden gels can deliver CyA at therapeutic dosages for a period of about 20 days. Release of the drug is diffusion controlled with effective diffusivities decreasing with increasing surfactant loading. The release kinetics are relatively similar for both surfactant and microemulsion-laden gels with comparable surfactant loading. The results also show that these hydrogels retain their effectiveness even after exposure to all the relevant processing conditions including unreacted monomer extraction, autoclaving and packaging, and so these materials seem to be very promising for ophthalmic delivery of CyA and perhaps other drugs.
Article
We used an animal model to compare the corneal and aqueous penetration of topical prednisolone acetate 1% with and without the presence of a commercially available collagen corneal shield. A significant (P less than .02) increase in penetration into cornea and aqueous humor at 30 minutes and 120 minutes was found in eyes with a collagen corneal shield in place. Increased concentrations were achieved by soaking the shield in prednisolone acetate for 15 minutes prior to application.
Article
Current therapeutic regimens for external ocular infections require instillation of antibiotics up to every quarter of an hour in concentrations higher than those commercially available. As an alternative to topically applied gentamicin eye drops, the possibility of sustained gentamicin release by bandage contact lenses was investigated. Ten hydrogel bandage contact lenses (61.4% HEMA and 38.6% water content) were soaked overnight in a 0.5% solution of sterile, unpreserved, commercially available gentamicin, and fitted thereafter on ten eyes of healthy adult volunteers. Gentamicin concentrations in the tear film were determined 10, 30, and 60 minutes, and 4, 8, 24, 48, 72, and 96 hours after fitting, using agar diffusion bioassay. Bactericidal concentrations (greater than 1.6 micrograms/ml) were found up to 3 days after contact lens fitting in all subjects. No toxic topical or systemic effects were seen.
Article
The potential of Gelfoam absorbable gelatin sponge as a carrier for ophthalmic delivery of pilocarpine was examined. Prolonged in vitro release of pilocarpine was achieved through pharmaceutical modification of the device by embedding a retardant in the pores. The device embedded with cetyl ester wax released pilocarpine in a zero-order pattern (release exponent = 0.93 +/- 0.04) for up to 5 hr. This result corresponded well with a linear penetrant uptake by this device. The device impregnated with polyethylene glycol 400 monostearate exhibited anomalous drug transport with a release exponent of 0.63 +/- 0.02. The absorption of water by this retardant and the formation of a gel layer on the surface slowed the penetration of the release medium into the deeper sections of the matrix, as well as the rapid outward diffusion of drug, resulting in a prolonged release of pilocarpine.
Article
To report a case of corneal ulcer associated with deposits of norfloxacin. Case report. A 40-year-old man with right trigeminal and facial nerve palsies and decreased tear secretion developed a corneal ulcer with white deposits in the right eye. The deposits were removed and analyzed by high-performance liquid chromatography. High-performance liquid chromatography results disclosed that the deposits on the corneal surface had the same retention time as norfloxacin. The patient discontinued norfloxacin ophthalmic solution and recovered successfully. Clinicians should be aware that frequent applications of topical norfloxacin in patients with decreased tear secretion may result in deposition of the drug on the cornea.