ArticleMolecular pharmaceutics2012
Hydrophilic prodrug approach for reduced pigment binding and enhanced transscleral retinal delivery of celecoxib.
Article in Molecular pharmaceutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed, 12 citations in OpenAlex.
- Promising Role of Silk-Based Biomaterials for Ocular-Based Drug Delivery and Tissue Engineering.Polymers · 2022Review
- Therapeutic implications of nanomedicine for ocular drug delivery.Drug discovery today · 2019Review
- Controlled release of corticosteroid with biodegradable nanoparticles for treating experimental autoimmune uveitis.Journal of controlled release : official journal of the Controlled Release Society · 2019Article
- Transporter targeted gatifloxacin prodrugs: synthesis, permeability, and topical ocular delivery.Molecular pharmaceutics · 2012Article
Corrections and comments
- Retraction · 2015-06-01Ethical Violations by Author · Falsification/Fabrication of Data · Investigation by Company/Institution · Misconduct - Official Investigation(s) and/or Finding(s) ·
- Commented on by
- Retracted
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Transscleral retinal delivery of celecoxib, an anti-inflammatory and anti-VEGF agent, is restricted by its poor solubility and binding to the melanin pigment in choroid-RPE. The purpose of this study was to develop soluble prodrugs of celecoxib with reduced pigment binding and enhanced retinal delivery. Three hydrophilic amide prodrugs of celecoxib, celecoxib succinamidic acid (CSA), celecoxib maleamidic acid (CMA), and celecoxib acetamide (CAA) were synthesized and characterized for solubility and lipophilicity. In vitro melanin binding to natural melanin (Sepia officinalis) was estimated for all three prodrugs. In vitro transport studies across isolated bovine sclera and sclera-choroid-RPE (SCRPE) were performed. Prodrug with the highest permeability across SCRPE was characterized for metabolism and cytotoxicity and its in vivo transscleral delivery in pigmented rats. Aqueous solubilities of CSA, CMA, and CAA were 300-, 182-, and 76-fold higher, respectively, than celecoxib. Melanin binding affinity and capacity were significantly lower than for celecoxib for all three prodrugs. Rank order for the % in vitro transport across bovine sclera and SCRPE was CSA > CMA ~ CAA ~ celecoxib, with the transport being 8-fold higher for CSA than celecoxib. CSA was further assessed for its metabolic stability and in vivo delivery. CSA showed optimum metabolic stability in all eye tissues with only 10-20% conversion to parent celecoxib in 30 min. Metabolic enzymes responsible for bioconversion included amidases, esterase, and cytochrome P-450. In vivo delivery in pigmented BN rats showed that CSA had 4.7-, 1.4-, 3.3-, 6.0-, and 4.5-fold higher delivery to sclera, choroid-RPE, retina, vitreous, and lens than celecoxib. CSA has no cytotoxicity in ARPE-19 cells in the concentration range of 0.1 to 1000 μM. Celecoxib succinamidic acid, a soluble prodrug of celecoxib with reduced melanin binding, enhances transscleral retinal delivery of celecoxib.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.