Platform For Ocular Drug Delivery Research Articles

Daily disposable contact lenses as a platform for ocular drug delivery of cyclosporine A

Ophthalmic drug delivery is an important area of research that aims to improve the efficacy and convenience of treatment for various eye conditions. There are multiple ways in which drugs can be delivered to the eye, including eye drops, ointments, gels, and inserts. The most prevalent way of administering medication to the eye is through eye drops. They are easy to use and can be self-administered by patients. Nonetheless, eye drops have the disadvantage of being prone to removal by tears, which may result in insufficient drug absorption and reduced effectiveness. Irregular use of active substances can exacerbate the disease, resulting in prolonged treatment with questionable efficacy. Soft contact lenses that serve as ophthalmic drug delivery systems (DDS) can become a viable substitute for traditional treatments. These polymeric lenses can be embedded with various active compounds, some of which are not readily soluble in water or physiological fluids. One such drug is Cyclosporine A (CyA), an immunosuppressant with a high molecular weight and hydrophobic properties, chronically used to treat dry eye syndrome (DES). The article discusses the development of a method for modifying Hilafilcon B contact lenses obtained from drugstores with Cyclosporine A (CyA). The drug was administered to the lenses using an immersion technique, and the process parameters were monitored to control drug release efficiency and profile. The drug release was measured in an Artificial Lacrimal Fluid (ALF) buffer, mimicking tear fluid with a pH of 7.9. The stability of CyA in this buffer was assessed. For the parameters used, the best drug application and release profile was achieved by immersing the contact lenses for 24 hours at 25 °C in a CyA solution containing 20 μg/ml of the active substance and adding 5 mg/ml of Vitamin E.

Real-Time Monitoring Platform for Ocular Drug Delivery.

Real-time measurement is important in modern dissolution testing to aid in parallel drug characterisation and quality control (QC). The development of a real-time monitoring platform (microfluidic system, a novel eye movement platform with temperature sensors and accelerometers and a concentration probe setup) in conjunction with an in vitro model of the human eye (PK-Eye™) is reported. The importance of surface membrane permeability when modelling the PK-Eye™ was determined with a "pursing model" (a simplified setup of the hyaloid membrane). Parallel microfluidic control of PK-Eye™ models from a single source of pressure was performed with a ratio of 1:6 (pressure source:models) demonstrating scalability and reproducibility of pressure-flow data. Pore size and exposed surface area helped obtain a physiological range of intraocular pressure (IOP) within the models, demonstrating the need to reproduce in vitro dimensions as closely as possible to the real eye. Variation of aqueous humour flow rate throughout the day was demonstrated with a developed circadian rhythm program. Capabilities of different eye movements were programmed and achieved with an in-house eye movement platform. A concentration probe recorded the real-time concentration monitoring of injected albumin-conjugated Alexa Fluor 488 (Alexa albumin), which displayed constant release profiles. These results demonstrate the possibility of real-time monitoring of a pharmaceutical model for preclinical testing of ocular formulations.

Photo-Responsive Hydrogel Microneedles With Interlocking Control for Easy Extraction in Sustained Ocular Drug Delivery

Abstract Microneedle arrays provide a minimally invasive platform for ocular drug delivery. Self-adhesive microneedle arrays, which incorporate barb-like locking features, have been developed to secure the array in place without using any adhesive. However, these locking features may increase extraction forces when removing the microneedle array once the drug delivery is completed. In this study, we demonstrated a photoresponsive hydrogel microneedle array that can self-adhere to the application site upon swelling and can deswell for easy removal when illuminated with light. The photoresponsive hydrogel microneedle arrays were made by a mixture of polyvinyl alcohol and spiropyran-conjugated N-isopropylacrylamide (NIPPAM). Experimental results show a significant decrease in extraction force after the microneedle of 20% spiropyran-conjugated NIPPAM was illuminated with light for 15 min. At the same time, the width of the interlocking feature also deswelled by 20% due to the photoresponsive behavior. However, the addition of the spiropyran-conjugated NIPPAM also weakens the mechanical properties of the microneedle and thus increase in insertion force.

Kaempferol Incorporated Bovine Serum Albumin Fibrous Films for Ocular Drug Delivery.

The possibility of using drug loaded bovine serum albumin (BSA) porous films as therapeutic contact lenses is investigated. Kaempferol (KAE), a hydrophobic antioxidant and anti-inflammatory agent, is incorporated into BSA porous films to form BSA/KAE films. The BSA/KAE films are transparent in the visible wavelength range of the human eye, possessing high water content and good cytocompatibility. A prolonged and sustained drug release is observed, and the in vivo efficacy of BSA/KAE films is better than the individual KAE. BSA/KAE films promoted the corneal re-epithelialization, inhibited neovascularization, and reduced the inflammation of an alkali burn induced corneal injury model. The study demonstrates the promising potential of BSA/KAE films as therapeutic contact lenses for the treatment of corneal injury, builds an available ocular drug delivery platform for ocular diseases.

Steroid-eluting contact lenses for corneal and intraocular inflammation

Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery. Statement of SignificanceInflammation of the eye can happen either on the ocular surface (i.e. the cornea) or inside the eye, both of which can result in loss of vision or even blindness. Ocular inflammation is normally treated by steroid eye drops. Depending on the type and severity of inflammation, patients may have to take drops every hour for days at a time. Such severe dosing regimen can lead to patients missing doses. Also, more than 95% drug in an eye drop never goes inside the eye. Here we present a contact lens that release a steroid (dexamethasone) for seven days at a time. It is much more efficient than eye drops and a significant improvement since once worn, the patient will avoid missing doses.

Development and evaluation of performance characteristics of timolol-loaded composite ocular films as potential delivery platforms for treatment of glaucoma

Thin and erodible polymeric films were developed as potential ocular drug delivery systems to increase drug retention on the eye with the aim of improving bioavailability and achieving controlled drug release. Two biocompatible film forming polymers, hyaluronic acid (HA) and hydroxypropyl methylcellulose (HPMC), which are currently used as thickening agents in eye drops were employed. Two different films were prepared (i) as single polymer and (ii) as composite formulations by solvent casting method, incorporating glycerol (GLY) as plasticizer and timolol maleate (TM) as model glaucoma drug. After preliminary optimization of transparency and ease of handling, the formulations were further characterized for their physicochemical properties. No indication of significant drug-polymer or polymer-polymer (in composite films) interaction was observed from FTIR results while evaluation by IR mapping revealed uniform distribution of drug throughout the films. Amorphization of TM in the film matrix was confirmed by both DSC and XRD. Swelling studies illustrated remarkable swelling capacity of HA in comparison with HPMC which directly affected the drug release profiles, making HA a suitable polymer for controlled ocular drug delivery. Tensile and mucoadhesion properties confirmed higher elasticity and adhesiveness of HA while HPMC produced stronger films. The effect of sterilization by UV radiation on mechanical properties was also evaluated and showed no significant difference between the sterilized and non-sterilized films. The SEM results confirmed smoothness and homogeneity of film surfaces for all the formulations studied. The in vitro drug dissolution studies showed more extended release profiles of formulations containing HA. Cytotoxicity study (cell viability) using MTT assay on HeLa cells, confirmed that the single polymer and composite films are generally safe for ocular administration. The present work shows excellent film forming ability of HA and HPMC which can be used as single polymer or combined in composite formulations as potential topical ocular drug delivery platform to enhance drug retention on the ocular surface and therefore potential improved bioavailability.

A hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier ocular drug delivery platform

The objective of this study was to develop a novel hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier (NLC) drug delivery platform. An ophthalmic anti-inflammatory drug, baicalin (BN) was chosen as the model drug. BNNLC was prepared using melt-emulsification combined with ultra-sonication technique. Additionally, a dual pH- and thermo-sensitive hydrogel composed of carboxymethyl chitosan (CMCS) and poloxamer 407 (F127) was fabricated by a cross-linking reaction with a nontoxic crosslinker genipin (GP). GP-CMCS/F127 hydrogel was characterized by FTIR, NMR, XRD and SEM. The swelling studies showed GP-CMCS/F127 hydrogel was both pH- and thermo-sensitive. The results of in vitro release suggested BNNLC gel can prolong the release of baicalin comparing with BN eye drops and BNNLC. Ex vivo cornea permeation study was evaluated using Franz diffusion cells. The apparent permeability coefficient (Papp) of BNNLC gel was much higher (4.46-fold) than that of BN eye drops. Through the determination of corneal hydration levels, BNNLC gel was confirmed that had no significant irritation to cornea. Ex vivo precorneal retention experiments were carried out by a flow-through approach. The results indicated that the NLC-based hydrogel can prolong precorneal residence time. In conclusion, the hybrid NLC-based hydrogel has a promising potential for application in ocular drug delivery.

In situ formation of injectable chitosan-gelatin hydrogels through double crosslinking for sustained intraocular drug delivery

Rapid clearance and low ocular bioavailability are drawbacks of conventional ophthalmic eye drops. To increase the ocular drug resistance time and improve efficacy, an in situ forming and thermosensitive chitosan-gelatin hydrogel was developed. The feasibility of using this hydrogel as a topical eye drop formulation for sustained release of timolol maleate was evaluated. The flexible hydrogel that was co-crosslinked with β‑glycerophosphate disodium salt hydrate (β-GD) and genipin showed a fast gel formation at 37 °C. The swelling properties and in vitro biodegradation characteristics showed a strong relationship with the initial genipin concentration. In vitro release profiles demonstrated that crosslinking with genipin reduced the release rate of entrapped model drugs and timolol maleate. In vitro cytotoxicity tests showed that the hydrogel was non-toxic to Chinese hamster fibroblast V79 cells. The hydrogel was further applied as eye drop formulations for sustained release of timolol maleate to reduce intraocular pressure (IOP). A fast gel formation was observed after instilling the chitosan-gelatin solution into the lower conjunctival sac of the rabbit eyes, and the in situ formed hydrogels protected the drugs from clearance by tears, and released the drugs in a sustained manner. Furthermore, administration of timolol maleate containing chitosan-gelatin hydrogels showed a long-lasting and effective IOP lowering efficacy for up to 24 h compared with the conventional eye drops. These results suggested that β-GD and genipin co-crosslinked chitosan-gelatin hydrogels could be a useful ocular drug delivery platform with enhanced therapeutic effects and reduced side effects.

Adherence of Pseudomonas aeruginosa onto surfactant-laden contact lenses

There is an immense research interest to utilise contact lens (CLs) as a popular platform for ocular drug delivery. However, CLs are the major predisposing factors of bacterial keratitis which is commonly caused by adhesion of microbes such as Pseudomonas aeruginosa and Staphylococcus epidermidis. The aim of the current study is to explore the effect of surfactants; Poloxamer 188, Polysorbate 80 and Tetronic® 90R4 (at 0.25% – 3% v/v) on the characteristics of CLs and on the adhesion abilities of Pseudomonas aeruginosa to the lenses’ surfaces. CLs were formulated using a hydrophilic monomer; 2-hydroxyethyl methacrylate (HEMA) together with silicone-based polymer such as Poly dimethyl siloxane (PDMS) or 3,3,3-trifluoropropylsilane (FSA) then lenses were polymerized under UV light. The formulated CLs with surfactants were found to have an increased equilibrium water content (EWC) due to hydrophilic moiety present in surfactants. A relationship was deduced between EWC and surface contact angle of lenses containing surfactants; where an increased EWC was associated with a decrease in contact angle reflecting a more hydrophilic surfaces of CLs. Apart from the 3% Polysorbate 80 (p < .0001) CLs, all other formulations had light transmission values over 80%. Lenses with surfactants were found to have lower bacterial ATP concentration than lenses without surfactants. Poloxamer 188 in FSA lenses reduced bacterial adhesion from 4.22 × 10−4 ± 1.30 × 10−4 pM to 1.03 × 10−4 ± 4.86 × 10−5 pM, a reduction by 75.59% when compared to the control lenses (p = .002). Moreover, 1% Tetronic® 90R4 in PDMS showed a reduction by 57.17% in ATP concentration. Polysorbate 80 in FSA exhibited the least bacterial adhesion with an average bacterial ATP concentration of 3.85 × 10−5 ± 2.61 × 10−5 pM; i.e 90.88% less bacterial ATP than control lenses (p = .001). Bioluminescence studies demonstrated a decrease in Pseudomonas aeruginosa adhesion to CLs containing surfactants without impairing the optical and mechanical characteristics of the lenses.

Chitosan Nanoparticles as a Mucoadhesive Drug Delivery System for Ocular Administration.

Pharmaceutical approaches based on nanotechnologies and the development of eye drops composed of the mucoadhesive polymers chitosan and hyaluronic acid are emerging strategies for the efficient treatment of ocular diseases. These innovative nanoparticulate systems aim to increase drugs’ bioavailability at the ocular surface. For the successful development of these systems, the evaluation of mucoahesiveness (the interaction between the ocular delivery system and mucins present on the eye) is of utmost importance. In this context, the aim of the present work was to investigate the mucoadhesivity of a novel nanoparticle eye drop formulation containing an antibiotic (ceftazidime) intended to treat eye infections. Eye drop formulations comprised a polymer (hydroxypropyl) methyl cellulose (HPMC) 0.75% (w/v) in an isotonic solution incorporating chitosan/sodium tripolyphosphate (TPP)-hyaluronic acid-based nanoparticles containing ceftazidime. The viscosity of the nanoparticles, and the gels incorporating the nanoparticles were characterized in contact with mucin at different mass ratios, allowing the calculation of the rheological synergism parameter (∆η). Results showed that at different nanoparticle eye formulation:mucin weight ratios, a minimum in viscosity occurred which resulted in a negative rheological synergism. Additionally, the results highlighted the mucoadhesivity of the novel ocular formulation and its ability to interact with the ocular surface, thus increasing the drug residence time in the eye. Moreover, the in vitro release and permeation studies showed a prolonged drug release profile from the chitosan/TPP-hyaluronic acid nanoparticles gel formulation. Furthermore, the gel formulations were not cytotoxic on ARPE-19 and HEK293T cell lines, evaluated by the metabolic and membrane integrity tests. The formulation was stable and the drug active, as shown by microbiological studies. In conclusion, chitosan/TPP-hyaluronic acid nanoparticle eye drop formulations are a promising platform for ocular drug delivery with enhanced mucoadhesive properties.

Melt-Cast Noninvasive Ocular Inserts for Posterior Segment Drug Delivery

The objective of the present study was to evaluate the utility of melt-cast, topical, ocular inserts for delivery of drugs with different physicochemical properties. The model drugs tested include indomethacin (IN), ciprofloxacin hydrochloride, and prednisolone sodium phosphate. Melt-cast method was used to fabricate ophthalmic inserts. Polyethylene oxide N10, a semicrystalline thermoplastic polymer (polyethylene oxide N10; Mol. wt: 100 kDa) was used as the matrix-forming material. Polymeric insert units (4 × 2 × 0.2 mm) with a 10% w/w drug load were tested for in vitro release, transmembrane permeability, and in vivo ocular tissue distribution. Marketed ophthalmic solutions were used as control solutions. Drug content in all the formulations ranged between 93% and 102% of the theoretical value. Transmembrane flux of IN, prednisolone sodium phosphate, and ciprofloxacin hydrochloride was enhanced by ∼3.5-folds, ∼3.6-folds, and ∼2.9-folds, respectively, from the polymeric inserts compared with the control formulations, after 3 h. Moreover, ocular inserts generated significantly higher drug levels in all the ocular tissues, including the retina-choroid, compared with their control formulations. The melt-cast ophthalmic inserts show promise as an effective noninvasive ocular drug delivery platform, which will be highly beneficial in the intervention and treatment of a wide variety of ocular complications.

Preparation and evaluation of PLGA nanoparticle-loaded biodegradable light-responsive injectable implants as a promising platform for intravitreal drug delivery

The present study reports on the development of a hybrid system by integrating poly(lactic-co-glycolic)acid nanoparticles (PLGA NPs) into light-responsive in-situ forming injectable implants (ISFIs) for minimally invasive and safe intravitreal peptide delivery. In the first part of the study, peptide-loaded PLGA based nanoparticles (NPs) were developed using the two-step nanoprecipitation technique. Peptide compatibility with PLGA and polyvinyl alcohol was confirmed via IR spectroscopy. Developed NPs had a size of 149.3–235.4 nm, a polydispersity index between 0.24 and 0.46, a zeta potential of −32.4 to −27.0 mV and an entrapment efficiency of 34.3–55.3%. In the second part of the study, successful synthesis of methacrylated alginate (MA) and its subsequent photocrosslinking upon photoirridiation was confirmed by 1H NMR. Photocrosslinked MA exhibited the required clarity and its gelling time, morphology, syringeability, hardness, rate of swelling and degradation were found suitable for prolonging its residence in the posterior segment. The sulforhodamine B assay on human retinal pigment epithelium cells and the zebrafish embryo toxicity test confirmed the biocompatibility of NPs and ISFIs. Finally, NPs were incorporated into the ISFIs for improved particle retention and to further sustain drug release, suggesting the proposed hybrid system as an innovative and efficient ocular drug delivery platform.

Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys

To assess the ability of latanoprost-eluting contact lenses to lower the intraocular pressure (IOP) of glaucomatous eyes of cynomolgus monkeys. Preclinical efficacy study of 3 treatment arms in a crossover design. Female cynomolgus monkeys with glaucoma induced in 1 eye by repeated argon laser trabeculoplasty. Latanoprost-eluting low-dose contact lenses (CLLO) and high-dose contact lenses (CLHI) were produced by encapsulating a thin latanoprost-polymer film within the periphery of a methafilcon hydrogel, which was lathed into a contact lens. We assessed the IOP-lowering effect of CLLO, CLHI, or daily latanoprost ophthalmic solution in the same monkeys. Each monkey consecutively received 1 week of continuous-wear CLLO, 3 weeks without treatment, 5 days of latanoprost drops, 3 weeks without treatment, and 1 week of continuous-wear CLHI. On 2 consecutive days before initiation of each study arm, the IOP was measured hourly over 7 consecutive hours to establish the baseline IOP. Two-tailed Student t tests and repeated-measures analysis of variance were used for statistical analysis. Intraocular pressure. Latanoprost ophthalmic solution resulted in IOP reduction of 5.4±1.0 mmHg on day 3 and peak IOP reduction of 6.6±1.3 mmHg on day 5. The CLLO reduced IOP by 6.3±1.0, 6.7±0.3, and 6.7±0.3 mmHg on days 3, 5, and 8, respectively. The CLHI lowered IOP by 10.5±1.4, 11.1±4.0, and 10.0±2.5 mmHg on days 3, 5, and 8, respectively. For the CLLO and CLHI, the IOP was statistically significantly reduced compared with the untreated baseline at most time points measured. The CLHI demonstrated greater IOP reduction than latanoprost ophthalmic solution on day 3 (P= 0.001) and day 5 (P= 0.015), and at several time points on day 8 (P < 0.05). Sustained delivery of latanoprost by contact lenses is at least as effective as delivery with daily latanoprost ophthalmic solution. More research is needed to determine the optimal continuous-release dose that would be well tolerated and maximally effective. Contact lens drug delivery may become an option for the treatment of glaucoma and a platform for ocular drug delivery.

Assessment of alkoxylphenacyl-based polycarbonates as a potential platform for controlled delivery of a model anti-glaucoma drug

Treatment strategies for glaucoma will benefit from injectable and/or implantable delivery systems that can achieve sustained delivery of neuroprotective agents (to the posterior segment) and/or intraocular pressure lowering drugs (to the anterior segment). In this regard, we have evaluated the suitability of a new polymer (alkoxylphenacyl-based polycarbonates copolymer with polycaprolactone; AP-PCL 20% w/w) as a platform for ocular drug delivery. Brimonidine tartrate (BRT) was applied as a model anti-glaucoma drug. The polymer was applied to develop injectable (nanoparticles) and implantable (microfilms) delivery systems. Nanoparticles fabricated from AP-PCL were stable and have an average size less than 200nm. The AP-PCL microfilms prepared by compression molding showed a gradual hydrolytic in-vitro degradation monitored by water uptake, weight loss, microscopy, DSC and FT-IR measurements. AP-PCL microfilms achieve sustained delivery of BRT for up to 90days. Biocompatibility of AP-PCL-based delivery systems was demonstrated from studies in human trabecular meshwork cell line as well as after intravitreal injections in rats. The overall trend demonstrated that AP-PCL delivery systems may be considered as suitable candidates for prolonged drug delivery in chronic ocular disorders such as glaucoma.

Thermo-Responsive Hydrogels for Ocular Drug Delivery.

Hydrogel as an ocular drug delivery platform holds great potential. Hydrogels are three-dimensional, hydrophilic, polymeric networks capable of absorbing large amounts of water or biological fluids. They have the ability to swell in an aqueous solvent system, holding solvents within a cross-linked gel system for potential sustained delivery. Through manipulation of permeation and diffusion characteristics, they can retain hydrophobic and hydrophilic agents, small molecules and macromolecules. In addition, hydrogel can be combined with nano- or microspheres to enhance delivery capacity. The aqueous environment of hydrogels can also protect cells and pharmacological agents. Depending on the specific structure, they can be nondegradable or degradable in their application.

Polyamidoamine dendrimer hydrogel for enhanced delivery of antiglaucoma drugs

Dendrimer hydrogel (DH), made from ultraviolet-cured polyamidoamine dendrimer G3.0 tethered with three polyethylene glycol (PEG, 12,000 Da)–acrylate chains (8.1% w/v) in pH 7.4 phosphate buffered saline (PBS), was studied for the delivery of brimonidine (0.1% w/v) and timolol maleate (0.5% w/v), two antiglaucoma drugs. DH was found to be mucoadhesive to mucin particles and nontoxic to human corneal epithelial cells. DH increased the PBS solubility of brimonidine by 77.6% and sustained the in vitro release of both drugs over 56–72 hours. As compared to eye drop formulations (PBS-drug solutions), DH brought about substantially higher human corneal epithelial cells uptake and significantly increased bovine corneal transport for both drugs. DH increased timolol maleate uptake in bovine corneal epithelium, stroma, and endothelium by 0.4- to 4.6-fold. This work demonstrated that DH can enhance the delivery of antiglaucoma drugs in multiple aspects and represents a novel platform for ocular drug delivery. From the Clinical EditorDendrimer hydrogel was studied as agent for simultaneous delivery of two anti-glaucoma drugs, one hydrophobic and one hydrophilic. Superiority over standard PBS-based formulation was clearly demonstrated for both drugs. The work may be a novel platform for ocular drug delivery.

The effects of cross-linked thermo-responsive PNIPAAm-based hydrogel injection on retinal function

There is significant interest in biomaterials that provide sustained release of therapeutic molecules to the retina. Poly( N-isopropylacrylamide) (PNIPAAm)-based materials have received significant attention as injectable drug delivery platforms due to PNIPAAm’s thermo-responsive properties at approximately 32 °C. While the drug delivery properties of PNIPAAm materials have been studied extensively, there is a need to evaluate the safety effects of hydrogel injection on retinal function. The purpose of this study was to examine the effect of poly(ethylene glycol) diacrylate (PEG-DA) crosslinked PNIPAAm hydrogel injection on retinal function. Utilizing scanning laser ophthalmoscopy (SLO), optical coherent tomography (OCT), and electroretinography (ERG), retinal function was assessed following hydrogel injection. In region near the hydrogel, there was a significant decrease in arterial and venous diameters (∼4%) and an increase in venous blood velocity (∼8%) 1 week post-injection. Retinal thickness decreased (∼6%) at 1 week and the maximum a- and b-wave amplitudes of ERG decreased (∼15%). All data returned to baseline values after week 1. These data suggest that the injection of PEG-DA crosslinked PNIPAAm hydrogel results in a small transient effect on retinal function without any long-term effects. These results further support the potential of PNIPAAm-based materials as an ocular drug delivery platform.

A Drug-Eluting Contact Lens

To formulate and characterize a drug-eluting contact lens designed to provide extended, controlled release of a drug. Prototype contact lenses were created by coating PLGA (poly[lactic-co-glycolic acid]) films containing test compounds with pHEMA (poly[hydroxyethyl methacrylate]) by ultraviolet light polymerization. The films, containing encapsulated fluorescein or ciprofloxacin, were characterized by scanning electron microscopy. Release studies were conducted in phosphate-buffered saline at 37 degrees C with continuous shaking. Ciprofloxacin eluted from the contact lens was studied in an antimicrobial assay to verify antimicrobial effectiveness. After a brief and minimal initial burst, the prototype contact lenses demonstrated controlled release of the molecules studied, with zero-order release kinetics under infinite sink conditions for over 4 weeks. The rate of drug release was controlled by changing either the ratio of drug to PLGA or the molecular mass of the PLGA used. Both the PLGA and the pHEMA affected release kinetics. Ciprofloxacin released from the contact lenses inhibited ciprofloxacin-sensitive Staphylococcus aureus at all time-points tested. A prototype contact lens for sustained drug release consisting of a thin drug-PLGA film coated with pHEMA could be used as a platform for ocular drug delivery with widespread therapeutic applications.