ArticleInternational journal of nanomedicine2019
Energy-dependent endocytosis is responsible for drug transcorneal penetration following the instillation of ophthalmic formulations containing indomethacin nanoparticles.
Article in International journal of nanomedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 78 citations in OpenAlex.
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- Dermal formulation based on carbopol and Gum Arabic improves skin retention of indomethacin.PloS one · 2025Article
- Intravesical Tumor-Selective Mucoadhesive Hydrogel for Effective Chemotherapy In Murine Model.International journal of nanomedicine · 2025Article
- Enhancement of therapeutic efficacy of Brinzolamide for Glaucoma by nanocrystallization and tyloxapol addition.Journal of pharmaceutical health care and sciences · 2024Article
- PLL-g-PEG Polymer Inhibits Antibody-Drug Conjugate Uptake into Human Corneal Epithelial CellsJournal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2024Article
- Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis.The Journal of clinical investigation · 2024Article
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- Treatment of colorectal cancer by anticancer and antibacterial effects of hemiprotonic phenanthroline-phenanthrolineAsian journal of pharmaceutical sciences · 2023Article
- Recent Progress of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Ocular Drug Delivery Platforms.Pharmaceuticals (Basel, Switzerland) · 2023Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe previously found that ophthalmic formulations containing nanoparticles prepared by a bead mill method lead to an increase in bioavailability in comparison with traditional formulations (solution type). However, the transcorneal penetration pathway for ophthalmic formulations has not been explained yet. In this study, we investigated the mechanism of transcorneal penetration in the application of ophthalmic formulations containing indomethacin nanoparticles (IMC-NPs). MATERIALS AND
methodsIMC-NPs was prepared by the bead mill method. For the analysis of energy-dependent endocytosis, corneal epithelial (HCE-T) cell monolayers and removed rabbit cornea were thermoregulated at 4°C, where energy-dependent endocytosis is inhibited. In addition, for the analysis of different endocytosis pathways using pharmacological inhibitors, inhibitors of caveolae-mediated endocytosis (54 µM nystatin), clathrin-mediated endocytosis (40 µM dynasore), macropinocytosis (2 µM rottlerin) or phagocytosis (10 µM cytochalasin D) were used.
resultsThe ophthalmic formulations containing 35-200 nm sized indomethacin nanoparticles were prepared by treatment with a bead mill, and no aggregation or degradation of indomethacin was observed in IMC-NPs. The transcorneal penetration of indomethacin was significantly decreased by the combination of nystatin, dynasore and rottlerin, and the decreased penetration levels were similar to those at 4°C in HCE-T cell monolayers and rabbit cornea. In the in vivo experiments using rabbits, dynasore and rottlerin tended to decrease the transcorneal penetration of indomethacin (area under the drug concentration - time curve in the aqueous humor [AUC
conclusionWe found that three energy-dependent endocytosis pathways (clathrin-dependent endocytosis, caveolae-dependent endocytosis and macropinocytosis) are related to the trans-corneal penetration of indomethacin nanoparticles. In particular, the caveolae-dependent endocytosis is strongly involved.
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