Modern approaches to the ocular delivery of cyclosporine A

Agarwal, Priyanka; Rupenthal, Ilva D.

doi:10.1016/j.drudis.2016.04.002

Cited by 61 publications

(44 citation statements)

References 133 publications

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“…Due to its physiological protective mechanisms the achievement of therapeutic levels of the drugs into ocular tissues became an extremely arduous challenge, especially for drugs with high molecular weight and/or hydrophobic characteristic, such as Cyclosporine A (CyA), a macrocyclic polypeptide having MW 1202 Da, log Po/w = 1.4-3.0 and a water solubility less than 0.1 mg/mL [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Assembling Surfactants-Mucoadhesive Polymer Nanomicelles (ASMP-Nano) for Ocular Delivery of Cyclosporine-A

et al. 2020

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The physiological protective mechanisms of the eye reduce the bioavailability of topically administered drugs above all for those with high molecular weight and /or lipophilic characteristics, such as Cyclosporine A (CyA). The combined strategy based on the association of nanomicelles and mucoadhesive polymer seems promising since a limited number of commercial products containing CyA have been recently approved. The scope of this investigation was the design of Assembling Surfactants-Mucoadhesive Polymer Nanomicelles (ASMP-Nano), based on a binary system of two surfactants in combination with hyaluronic acid, and their biopharmaceutical evaluation. The optimisation of the ASMP-Nano in term of the amount of surfactants, CyA-loading and size determined the selection of the clear and stable Nano1HAB-CyA formulation containing 0.105% w/w CyA loaded-nanomicelles with a size of 14.41 nm. The nanostructured system had a protective effect towards epithelial corneal cells with a cell viability of more than 80%. It interacted with cellular barriers favouring the uptake and the accumulation of CyA into the cells as evidenced by fluorescent probe distribution, by hindering CyA permeation through reconstituted corneal epithelial tissue. In pharmacokinetics study on rabbits, the nanomicellar carrier prolonged the CyA retention time in the precorneal area mainly in presence of hyaluronic acid (HA), a mucoadhesive polymer.

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Section: Introductionmentioning

confidence: 99%

Assembling Surfactants-Mucoadhesive Polymer Nanomicelles (ASMP-Nano) for Ocular Delivery of Cyclosporine-A

et al. 2020

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“…It has been shown to inhibit the production and/or release of proinflammatory cytokines and to upregulate the release of anti-inflammatory cytokines [94,96]. Moreover, inhibites the apoptosis and the number of Fas-ligand expression in infiltrating lymphocytes of human conjunctival epithelial cells [96,97]. The U.S. FDA approved on 11 July 2016 the first …”

Section: Topical Immunomodulatorsmentioning

confidence: 99%

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

Nebbioso¹,

Regno²,

Gharbiya³

et al. 2017

Preprint

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The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome, because the tear film represents the interface between the eye and the environment. Despite having a multifactorial origin, the main risk factors for the emergence of the ocular disease are female gender and advanced age. Peer-reviewed version available at Int. J. Mol. Sci. 2017, 18, 1764 doi:10.3390/ijms18081764 2 Likewise, morphological changes in several glands and in chemical composition of their secretions such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors to maintain a condition of good health of the ocular anterior segment. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic infiammation that reflex on the ocular surface. However, it is one of the most commonly encountered disease in clinical practice and many other causes related to daily life and to lengthen the average life will contribute to the beginning. This review will consider how and what disorders of the ocular surface are responsible for a widespread pathology so. In the end, the most appropriate and new therapies will be briefly exposed according to the specific pathology.

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“…[1][2][3][4][5] However, topical administration remains the most preferred route of ocular drug delivery, because it is noninvasive, painless and convenient. 6 Topically applied drug/formulation may not only reach anterior tissues but also reach back-of-the-eye tissues. 7 Effective topical drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability.…”

Section: Introductionmentioning

confidence: 99%

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

Xu¹,

Xu²,

Gu³

et al. 2018

IJN

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Background To enhance ocular bioavailability, the traditional strategies have focused on prolonging precorneal retention and improving corneal permeability by nano-carriers with positive charge, thiolated polymer, absorption enhancer and so on. Glycylsarcosine (GS) as an active target ligand of the peptide tranpsporter-1 (PepT-1), could specific interact with the PepT-1 on the cornea and guide the nanoparticles to the treating site. Purpose The objective of the study was to explore the active targeting intercalated nanocomposites based on chitosan-glutathione-glycylsarcosine (CG-GS) and layered double hydroxides (LDH) as novel carriers for the treatment of mid-posterior diseases. Materials and methods CG-GS-LDH intercalated nanocomposites were prepared by the coprecipitation hydrothermal method. In vivo precorneal retention study, ex vivo fluorescence images, in vivo experiment for distribution and irritation were studied in rabbits. The cytotoxicity and cellular uptake were studied in human corneal epithelial primary cells (HCEpiC). Results CG-GS-LDH nanocomposites were prepared successfully and characterized by FTIR and XRD. Experiments with rabbits showed longer precorneal retention and higher distribution of fluorescence probe/model drug. In vitro cytological study, CG-GS-LDH nanocomposites exhibited enhanced cellular uptake compared to pure drug solution. Furthermore, the investigation of cellular uptake mechanisms demonstrated that both the active transport by PepT-1 and clathrin-mediated endocytosis were involved in the internalization of CG-GS-LDH intercalated nanocomposites. An ocular irritation study and a cytotoxicity test indicated that these nanocomposites produced no significant irritant effects. Conclusions The active targeting intercalated nanocomposites could have great potential for topical ocular drug delivery due to the capacity for prolonging the retention on the ocular surface, enhancing the drug permeability through the cornea, and efficiently delivering the drug to the targeted site.

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Modern approaches to the ocular delivery of cyclosporine A

Cited by 61 publications

References 133 publications

Assembling Surfactants-Mucoadhesive Polymer Nanomicelles (ASMP-Nano) for Ocular Delivery of Cyclosporine-A

Assembling Surfactants-Mucoadhesive Polymer Nanomicelles (ASMP-Nano) for Ocular Delivery of Cyclosporine-A

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

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