Contact lens as an emerging platform for ophthalmic drug delivery: A systematic review

Yang, Hongyu; Zhao, Ming; Xing, Dandan; Zhang, Jian; Fang, Ting; Zhang, Faxing; Nie, Zhihao; Liu, Yaming; Yang, Lihua; Li, Ji; Wang, Dongkai

doi:10.1016/j.ajps.2023.100847

Cited by 7 publications

(2 citation statements)

References 103 publications

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“…On the other hand, (c) drugs might successively cross the bulbar conjunctiva, the sclera, and the uvea, particularly the choroid, into the vitreous body [Figure 2]. The bulbar conjunctiva possesses relatively leaky epithelium, lacking tight junctions, thereby enabling the entry of not only low-molecular-weight substances but also larger hydrophilic drugs such as siRNAs and peptides [21]. Several transporters such as PEPT1, amino acid transporters, and MDR1 are recognized in the bulbar conjunctiva [Figure 3].…”

Section: In Extracellular Regionmentioning

confidence: 99%

Ocular Drug Delivery into the Eyes Using Drug-Releasing Soft Contact Lens

Tashima

2024

Future Pharmacology

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The impact of visual impairment, such as blindness, on quality of life is immeasurable. However, effective ocular drug delivery into the eyes has not yet been established, primarily due to the impermeability imposed by the blood–retinal barrier (BRB) based on the tight junctions and efflux transporters at the endothelium or the epithelium in oral or intravenous administration, as well as the dilution with tear fluid and excretion through the nasolacrimal duct in eye drop administration. Furthermore, intravitreous injections induce pain and fear in patients. Unmet medical needs persist in ocular diseases such as age-related macular degeneration and diabetic retinopathy. Therefore, innovative non-invasive administration methods should be developed. Drug-releasing soft contact lenses (DR-SCLs) affixed to the eye’s surface can continuously and locally deliver their loaded drugs to the eyes. The use of DR-SCLs is expected to greatly enhance the bioavailability and patient adherence to the drug regimen. It is known that several solute carrier (SLC) transporters are expressed in various parts of the eyes, including the cornea, the ciliary body, and the bulbar conjunctiva. Carrier-mediated transport through SLC transporters may occur in addition to passive diffusion. Moreover, nanoparticles can be loaded into DR-SCLs, offering various intelligent approaches based on modifications to induce receptor-mediated endocytosis/transcytosis or to control the loaded drug release within this delivery system. In this perspective review, I discuss the implementation and potential of DR-SCL-mediated ocular drug delivery, particularly focusing on low-molecular-weight compounds because of their fine distribution in living body, ease of handling, and ease of manufacturing.

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Section: In Extracellular Regionmentioning

confidence: 99%

Ocular Drug Delivery into the Eyes Using Drug-Releasing Soft Contact Lens

Tashima

2024

Future Pharmacology

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“…In the drug development process, many candidates fail to pass preclinical and clinical studies due to high cytotoxicity, low targeting efficiency and adverse pharmacokinetic effects. − To improve drug efficacy and reduce side effects, novel drug delivery systems (DDSs) have been developed for small molecules, peptides and proteins. − Among them, peptide-based DDSs have shown great clinical potential owing to their good biocompatibility, low toxicity, and high biological activity. , For example, peptide-drug conjugates enable precise molecular-targeted therapy at the cellular level and have been used clinically as diagnostic agents and anticancer drugs. , Peptide-based hydrogel DDS exhibits good biodegradability so that can be used for intratumoral, subcutaneous and ocular drug delivery. − Peptides capable of penetrating cell membranes, when combined with tumor-targeting peptides, can selectively transport toxins or prodrug molecules to specific tissues and cells, thereby enhancing therapeutic efficacy. − Moreover, peptides can be used for the treatment of various diseases through self-assembly − or the formation of nanoparticles . Despite the significant advantages of peptides in drug delivery, poor cell membrane permeability severely hinders the development of peptide-delivered drugs .…”

Section: Introductionmentioning

confidence: 99%

Predicting Peptide Permeability Across Diverse Barriers: A Systematic Investigation

Tan,

Liu,

Fang

et al. 2024

Mol. Pharmaceutics

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Peptide-based therapeutics hold immense promise for the treatment of various diseases. However, their effectiveness is often hampered by poor cell membrane permeability, hindering targeted intracellular delivery and oral drug development. This study addressed this challenge by introducing a novel graph neural network (GNN) framework and advanced machine learning algorithms to build predictive models for peptide permeability. Our models offer systematic evaluation across diverse peptides (natural, modified, linear and cyclic) and cell lines [Caco-2, Ralph Russ canine kidney (RRCK) and parallel artificial membrane permeability assay (PAMPA)]. The predictive models for linear and cyclic peptides in Caco-2 and RRCK cell lines were constructed for the first time, with an impressive coefficient of determination (R 2 ) of 0.708, 0.484, 0.553, and 0.528 in the test set, respectively. Notably, the GNN framework behaved better in permeability prediction with larger data sets and improved the accuracy of cyclic peptide prediction in the PAMPA cell line. The R 2 increased by about 0.32 compared with the reported models. Furthermore, the important molecular structural features that contribute to good permeability were interpreted; the influence of cell lines, peptide modification, and cyclization on permeability were successfully revealed. To facilitate broader use, we deployed these models on the user-friendly KNIME platform (https://github.com/ifyoungnet/PharmPapp). This work provides a rapid and reliable strategy for systematically assessing peptide permeability, aiding researchers in drug delivery optimization, peptide preselection during drug discovery, and potentially the design of targeted peptide-based materials.

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