Episcleral implants for topotecan delivery to the posterior segment of the eye Journal Article


Authors: Carcaboso, A. M.; Chiappetta, D. A.; Opezzo, J. A. W.; Höcht, C.; Fandino, A. C.; Croxatto, J. O.; Rubio, M. C.; Sosnik, A.; Abramson, D. H.; Bramuglia, G. F.; Chantada, G. L.
Article Title: Episcleral implants for topotecan delivery to the posterior segment of the eye
Abstract: PURPOSE. Intravenous or periocular topotecan has been proposed as new treatment modality for patients with advanced intraocular retinoblastoma, but systemic topotecan lactone exposure induced by both approaches may cause toxicity. The purpose of this study was to develop a topotecan-loaded ocular delivery system to minimize systemic exposure and achieve selective transscleral penetration. METHODS. Biocompatible polymer implants containing low (0.3 mg) or high (2.3 mg) topotecan load were manufactured and characterized in vitro. Adrenaline (500 mu g) was coloaded to induce local vasoconstriction in vivo in 2 of 4 animal groups. Implants were inserted into the episclera of rabbits, and topotecan (lactone and total) concentrations in ocular tissues and plasma were determined over a period of 48 hours. RESULTS. In vitro, implants released 30% to 50% of the loaded drug within 48 hours and 45% to 70% by day 10. In vivo, topotecan lactone was highly accumulated in locally exposed ocular tissues (ranging from 10(5) to 10(6) ng/g in sclera and choroid and 10(2) to 10(3) ng/g in retina) over 48 hours with all the formulations studied. Low vitreous topotecan lactone levels (approximately 5 ng/mL) were found in animals receiving concomitant local vasoconstriction and high load implants. Topotecan lactone concentrations in plasma and in contralateral eyes were minimal or undetectable as a marker of tissue selectivity of the proposed strategy. CONCLUSIONS. These studies may contribute to improving the efficacy and safety of chemotherapy treatments for retinoblastoma and may support the role of the local vasculature and tissues promoting drug clearance and local accumulation during transscleral drug delivery. (Invest Ophthalmol Vis Sci. 2010; 51: 2126-2134) DOI:10.1167/iovs.09-4050
Keywords: chemotherapy; carboplatin; in-vivo; sclera; solid tumors; intraocular retinoblastoma; phase-ii; drug-delivery; rabbits; microdialysis
Journal Title: Investigative Ophthalmology & Visual Science (IOVS)
Volume: 51
Issue: 4
ISSN: 0146-0404
Publisher: Association for Research in Vision and Ophthalmology  
Date Published: 2010-04-01
Start Page: 2126
End Page: 2134
Language: English
ACCESSION: ISI:000275995800043
DOI: 10.1167/iovs.09-4050
PROVIDER: wos
PUBMED: 19834044
Notes: --- - Article - "Source: Wos"
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  1. David H Abramson
    326 Abramson