Topical sustained drug delivery to the retina with a drug-eluting contact lens

Ross, Amy E.; Bengani, Lokendrakumar C.; Tulsan, Rehka; Maidana, Daniel E.; Salvador-Culla, Borja; Kobashi, Hidenaga; Kolovou, Paraskevi E.; Zhai, Hualei; Taghizadeh, Koli; Kuang, Liangju; Mehta, Manisha; Vavvas, Demetrios G.; Kohane, Daniel S.; Ciolino, Joseph B.

doi:10.1016/j.biomaterials.2019.119285

Cited by 87 publications

(61 citation statements)

References 72 publications

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“…Traces of all drugs were detected in the posterior segment, although not in the vitreous, which suggests a drug delivery pathway via the local vasculature. This hypothesis was supported by the study of Ross et al [120], who encapsulated a dexamethasone-eluting PLGA ring into a CL: the device sustained drug release for one week in vitro, and it reached therapeutic drug levels in the retina in vivo. In fact, the drug concentration in the choroid and retina was significantly higher than in the vitreous of a rabbit model.…”

Section: Posterior Segment Diseasesmentioning

confidence: 78%

“…The physical link of these implants to IOLs may overcome the problem and guarantee their correct positioning in the anterior chamber of the eye. Despite being more commonly applied on IOLs [23,27,[117][118][119], examples of incorporated reservoirs were also implemented on CLs [120][121][122][123][124][125][126]. Drug reservoirs are usually constituted of biodegradable polymers: the material must be biocompatible, and its degradation products should not cause chronic inflammation or toxicity in the ocular tissues [47].…”

Section: Drug Reservoirsmentioning

confidence: 99%

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Therapeutic Ophthalmic Lenses: A Review

2020

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An increasing incidence of eye diseases has been registered in the last decades in developed countries due to the ageing of population, changes in lifestyle, environmental factors, and the presence of concomitant medical conditions. The increase of public awareness on ocular conditions leads to an early diagnosis and treatment, as well as an increased demand for more effective and minimally invasive solutions for the treatment of both the anterior and posterior segments of the eye. Despite being the most common route of ophthalmic drug administration, eye drops are associated with compliance issues, drug wastage by lacrimation, and low bioavailability due to the ocular barriers. In order to overcome these problems, the design of drug-eluting ophthalmic lenses constitutes a non-invasive and patient-friendly approach for the sustained drug delivery to the eye. Several examples of therapeutic contact lenses and intraocular lenses have been developed, by means of different strategies of drug loading, leading to promising results. This review aims to report the recent advances in the development of therapeutic ophthalmic lenses for the treatment and/or prophylaxis of eye pathologies (i.e., glaucoma, cataract, corneal diseases, or posterior segment diseases) and it gives an overview of the future perspectives and challenges in the field.

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Section: Posterior Segment Diseasesmentioning

confidence: 78%

Section: Drug Reservoirsmentioning

confidence: 99%

Therapeutic Ophthalmic Lenses: A Review

2020

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“…Although this manuscript focuses on circuit-embedded contact lenses, guidance on minimizing corneal edema is also applicable to contact lenses that have other multiple components, such as drug-eluting lenses [51]. For ESCLs, embedments may inhibit ion transport across the lens, potentially adhering the lens to the ocular surface [52,53].…”

Section: Dklens = Lencasementmentioning

confidence: 99%

Central-to-peripheral corneal edema during wear of embedded-component contact lenses

Kim

Lin

Radke

2022

Contact Lens and Anterior Eye

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With active investigation underway for embedded-circuit contact lenses, safe oxygen supply of these novel lenses remains a question. Central-to-peripheral corneal edema for healthy eyes during wear of soft contact (SCL) and scleral lenses (SL) with embedding components is assessed. Methods: Various 2-dimensional (2D) designs of SL and SCL with embedded components are constructed on Comsol Multiphysics 5.5. Local corneal swelling associated with the designed lenses is determined by a recently developed 2D metabolic-swelling model. Settled central post-lens tear-film thicknesses (PoLTFs) are set at 400 μm and 3 μm for SL and SCL designs, respectively. Each lens design has an axisymmetric central and an axisymmetric peripheral embedment. Oxygen permeability (Dk) of the lens and the embedments ranges from 0 to 200 Barrer. Dimensions and location of the embedments are varied to assess optimal-design configurations to minimize central-to-peripheral corneal edema. Results: By adjusting oxygen Dk of the central embedment, the peripheral embedment, or the lens matrix polymer, corneal swelling is reduced by up to 2.5 %, 1.5 %, or 1.4 % of the baseline corneal thickness, respectively, while keeping all other parameters constant. A decrease in PoLTF thickness from 400 μm to 3 μm decreases corneal edema by up to 1.8 % of the baseline corneal thickness. Shifting the peripheral embedment farther out towards the periphery and towards the anterior lens surface reduces peak edema by up to 1.3 % and 0.6 % of the baseline corneal thickness, respectively.Conclusions: To minimize central-to-peripheral corneal edema, embedments should be placed anteriorly and far into the periphery to allow maximal limbal metabolic support and oxygen transport in the polar direction (i.e., the θ-direction in spherical coordinates). High-oxygen transmissibility for all components and thinner PoLTF thickness are recommended to minimize corneal edema. Depending on design specifications, less than 1 % swelling over the entire cornea is achievable even with oxygen-impermeable embedments.

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“…Since bioavailability of eye drop is <5%, the absorbed amount is estimated to be 75 lg per day for the postoperative fibrosis treatment of eyes (Zhong et al, 2011). Ocular bioavailability of drug loaded in soft contact lens (SCL) was >50% (Ross et al, 2019;Maulvi et al, 2020;Xue et al, 2020), so the required dose for SCLs will be approximately 150 lg per day, which was our targeted amount of PFD in SCLs.…”

Section: Introductionmentioning

confidence: 99%

Controllable release of pirfenidone by polyvinyl alcohol film embedded soft contact lenses in vitro and in vivo

Chong

et al. 2021

Drug Delivery

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To increase the amount of pirfenidone (PFD) loaded in polyvinyl alcohol (PVA) film embedded soft contact lens (SCL), and evaluate its function of sustaining delivery of drug in vitro and in vivo . Drug loading efficiency within PVA film and SCLs, drug release from SCLs in vitro , and the effects of parameters of SCLs and external environment on drug release in vitro were evaluated by ultraviolet–visible spectrophotometer at 312 nm. Safety of SCLs was evaluated in vitro by transformed human corneal epithelial cell. Safety in vivo was determined by optical coherence tomography and histology of anterior segment of rabbits. Drug release study in tear fluid and aqueous humor were measured by ultra-performance liquid chromatography. SCLs had smooth surface and were fit for experimental rabbits. Amount of PFD in PVA film and SCLs were 153.515 μg ± 12.508 and 127.438 μg ± 19.674, respectively, PFD in PVA film was significantly higher than SCLs ( p =.006) and closed to 150 μg (targeting amount of PFD to be loaded). Thickness of SCLs, molecular weight of PVA, and amount of PVA used in SCLs affected drug release in vitro significantly. Thickness of PVA film and amount of drug in SCLs had no effect on drug release rate in vitro . SCLs were safe in vitro and in vivo , PFD released from SCLs could be detected around 12 hours in tears and aqueous humor, and the concentration of drug was higher than eye drop at all detected time points while amount of PFD in SCLs was lower than eye drop. Drug loaded PVA film embedded SCLs may be a promising ocular drug delivery system.

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Topical sustained drug delivery to the retina with a drug-eluting contact lens

Cited by 87 publications

References 72 publications

Therapeutic Ophthalmic Lenses: A Review

Therapeutic Ophthalmic Lenses: A Review

Central-to-peripheral corneal edema during wear of embedded-component contact lenses

Controllable release of pirfenidone by polyvinyl alcohol film embedded soft contact lenses in vitro and in vivo

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