Contact lenses for pravastatin delivery to eye segments: Design and in vitro-in vivo correlations

Pereira-da-Mota, Ana F; Vivero-Lopez, María; Serramito, María; Díaz-Gómez, Luis; Serro, Ana Paula; Carracedo, Gonzalo; Huete-Toral, Fernando; Concheiro, Ángel; Álvarez-Lorenzo, Carmen

doi:10.1016/j.jconrel.2022.06.001

Cited by 16 publications

(19 citation statements)

References 76 publications

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“…The lower values recorded for resveratrol may be linked to the sampling time of 8 h, in which the CL is almost exhausted and clearance mechanisms may predominate. In this regard, resveratrol levels in eye tissues after 8 h wearing of CL M12 were higher than those recently reported for pravastatin sodium delivered from HEMA-based CL copolymerized with hydrophobic (ethylene glycol phenyl ether methacrylate) and amino-bearing (2-aminoethyl methacrylamide hydrochloride) monomers, which lead to pravastatin contents of 158.46 ± 31.8 ng/g in cornea and 1.53 ± 0.59 ng/g in sclera …”

Section: Resultscontrasting

confidence: 60%

“…In this regard, resveratrol levels in eye tissues after 8 h wearing of CL M12 were higher than those recently reported for pravastatin sodium delivered from HEMA-based CL copolymerized with hydrophobic (ethylene glycol phenyl ether methacrylate) and amino-bearing (2-aminoethyl methacrylamide hydrochloride) monomers, which lead to pravastatin contents of 158.46 ± 31.8 ng/g in cornea and 1.53 ± 0.59 ng/g in sclera. 68 Antioxidant Activity of Resveratrol Worn CLs. A DPPH assay was performed to evaluate the capacity of CL M12 to preserve the antioxidant activity of the resveratrol remaining in the polymeric network after the in vivo experiment.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…In vivo release profiles were constructed from the area under the curve of concentrations of resveratrol in tears versus time 68 and then compared to the in vitro release profiles recorded in the absence of proteins (Figure 8). In the first 30 min of the release, the process was faster in vitro than in vivo, probably because of the much more volume available in vitro (compared to the few microliters available on eye surface) which created a more intense concentration gradient.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Capability to predict in vivo behavior and quality assessment during production could strongly benefit from in vitro release tests that may provide biorelevant information. So far the few attempts to correlate in vivo and in vitro release from CLs pointed out that in vitro tests carried out with a small volume may be more predictive. ,, In the case of resveratrol, a minimum volume of 6 mL of NaCl 0.9% was chosen due to its low aqueous solubility in order to prevent a rapid saturation of the release medium that could create artifacts in the release profile (as explained in the in vitro release section).…”

Section: Resultsmentioning

confidence: 99%

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Phosphorylcholine-Based Contact Lenses for Sustained Release of Resveratrol: Design, Antioxidant and Antimicrobial Performances, and In Vivo Behavior

Vivero-Lopez

Pereira-da-Mota

Carracedo

et al. 2022

ACS Appl. Mater. Interfaces

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Design of advanced contact lenses (CLs) demands materials that are safe and comfortable for the wearers and that preserve the normal eye microbiota, avoiding chronic inflammation and biofilm development. This work aimed to combine the natural antibiofouling phosphorylcholine and the antioxidant and prebiotic resveratrol as integral components of CLs that may have the additional performance of preventing oxidative-stress related eye diseases. Different from previous uses of 2-methacryloyloxyethyl phosphorylcholine (MPC) as coating, we explored the feasibility of adding MPC at high proportions as a comonomer of 2-hydroxyethyl methacrylate (HEMA)-based hydrogels while still allowing for the loading of the hydrophobic resveratrol. Homogeneous distribution of MPC along the hydrogel depth (confirmed by Raman spectroscopy) notably increased solvent uptake and the proportion of free water while it decreased Young’s modulus. Relevantly, MPC did not hinder the uptake of resveratrol by CLs (>10 mg/g), which indeed showed network/water partition coefficients of >100. Protocols for CLs sterilization and loading of resveratrol under aseptic conditions were implemented, and the effects of tear proteins on resveratrol release rate were investigated. CLs sustained resveratrol release for more than 24 h in vitro, and sorption of albumin onto the hydrogel, although attenuated by MPC, slowed down the release. The combination of MPC and resveratrol reduced P. aeruginosa and S. aureus growth as tested in a novel hydrogel disk-agar interface biofilm growth setup. The developed CLs showed excellent anti-inflammatory properties and biocompatibility in in ovo and rabbit tests and provided higher and more prolonged levels of resveratrol in tear fluid, which favored resveratrol biodistribution in anterior and posterior eye segments compared to eye drops. Correlations between the release profiles of resveratrol in vitro and in vivo were assessed. Relevantly, the CLs preserved the antioxidant properties of resveratrol during the entire 8 h of wearing. In sum, CLs prepared with high proportion in MPC may help address safety and comfort requirements while having drug releasing capabilities.

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Section: Resultscontrasting

confidence: 60%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Phosphorylcholine-Based Contact Lenses for Sustained Release of Resveratrol: Design, Antioxidant and Antimicrobial Performances, and In Vivo Behavior

Vivero-Lopez

Pereira-da-Mota

Carracedo

et al. 2022

ACS Appl. Mater. Interfaces

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“…In this study, Pereira-da-Mota and colleagues proposed the use of an HEMA/EGPEM/APMA-based contact lens as an ocular delivery system for pravastatin. [94] The hydrogel contact lens presents a unique composition in that it highly mimics the hydrophobic and amino features of the HMG-CoA binding site. Findings from the study show that the drug delivered by the contact lens demonstrates excellent anti-inflammatory activity with great permeation throughout the anterior and posterior eye segments.…”

Section: Statin Drug Deliverymentioning

confidence: 99%

Smart molecules in ophthalmology: Hydrogels as responsive systems for ophthalmic applications

Kulbay,

Wu,

Truong

et al. 2024

Smart Molecules

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This comprehensive review delves into a unique intersection of hydrogels as smart molecules and their transformative applications in ophthalmology. Beginning with the foundational definition, properties, and classification of hydrogels, the review explores their synthesis and responsive capabilities. Specific applications examined encompass topical drug delivery, contact lenses, intravitreal drug delivery, ocular adhesives, vitreous substitutes, and cell‐based therapy. A methodical analysis, including an overview of relevant ocular structures and a comparative evaluation of hydrogel‐based solutions against traditional treatments, is conducted. Additionally, potential constraints, translation challenges, knowledge gaps, and research areas are identified. Our methodical approach, guided by an extensive literature review from 2017 to 2023, illuminates the unprecedented opportunities offered by hydrogels, along with pinpointing areas for further inquiry to facilitate their transition into clinical practice.

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A Physiology-Based Mathematical Model to Understand Drug Delivery from Contact Lenses to the Back of the Eye

Toffoletto¹,

Santos²,

Serro³

et al. 2023

Pharm Res

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Objective Therapeutic contact lenses, able to store drug and deliver it to the eye surface in a sustained fashion, gained interest as an effective and patient-friendly alternative to eye drops. Recent animal studies also demonstrated the presence of therapeutic drug levels in the back of the eye after wearing drug-loaded contact lenses, thus opening the possibility of treating the posterior segment without need of invasive intraocular injections. The drug pathways from contact lenses to the back of the eye require further investigation. Methods A mechanistic mathematical model was developed to evaluate the drug concentration over time in the tears, sclera and choroid, retina, aqueous humor and vitreous humor after the application of a therapeutic contact lens. The main drug transport mechanisms of the eye and the barrier properties of the different tissues were included in the model. Validation was performed by comparison with experimental data in literature. Results The model predictions of drug concentration over time reflected the experimental data both in the anterior and posterior segment of the eye. The model can differentiate between contributions to transport from different pathways. Conclusions The model constitutes a first step towards the possibility of predicting the ocular drug distribution and the treatment efficacy in the early stage of contact lens development, and it may help reduce both the need for in vivo tests (with ethical and economic advantages) and the gap between the lens design and clinical application. It also allows for an improved understanding of drug transport in the eye. Graphical abstract

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Contact lenses for pravastatin delivery to eye segments: Design and in vitro-in vivo correlations

Cited by 16 publications

References 76 publications

Phosphorylcholine-Based Contact Lenses for Sustained Release of Resveratrol: Design, Antioxidant and Antimicrobial Performances, and In Vivo Behavior

Phosphorylcholine-Based Contact Lenses for Sustained Release of Resveratrol: Design, Antioxidant and Antimicrobial Performances, and In Vivo Behavior

Smart molecules in ophthalmology: Hydrogels as responsive systems for ophthalmic applications

A Physiology-Based Mathematical Model to Understand Drug Delivery from Contact Lenses to the Back of the Eye

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