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Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 4/2006

01.04.2006 | Laboratory Investigation

Intravitreal implantation of the biodegradable cyclosporin A drug delivery system for experimental chronic uveitis

verfasst von: Xiaoguang Dong, Weiyun Shi, Gongqiang Yuan, Lixin Xie, Shenguo Wang, Ping Lin

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 4/2006

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Abstract

Purpose

The purpose was to evaluate the efficacy of the intravitreal implantation of the biodegradable cyclosporin A (CsA) drug delivery system (DDS) for experimental chronic uveitis.

Methods

The DDS was prepared by formulating CsA into glycolide-co-lactide-co-caprolactone copolymer (PGLC). Right eyes of 30 New Zealand white rabbits were used to establish a model of uveitis and randomized into control, intravitreal non-medicated DDS, oral CsA (15 mg/kg daily), and intravitreal CsA-PGLC DDS (each containing 2 mg CsA) groups. The progress of ocular inflammation, results of electroretinography, and histopathological examination of ocular, renal, and hepatic functions were recorded. Intravitreal CsA levels were measured in another 13 rabbits receiving an implant of the CsA-PGLC DDS.

Results

Chronic uveitis was successfully induced in all 30 eyes. The inflammation in the eyes with no treatment, non-medicated implant, and oral CsA was more severe than those with the CsA-PGLC DDS at each timepoint. The electroretinography b-wave was depressed much less in the CsA-PGLC DDS group than in the other three groups (p<0.05). No renal or hepatic tissue damage was found in eyes with the CsA-PGLC DDS. The mean intravitreal CsA level was 102.2∼145.5 ng/ml at 1∼3 weeks after CsA-PGLC DDS implantation, 491.0∼575.2 ng/ml at 4∼10 weeks, and 257.3 ng/ml at 14 weeks; no toxicity was detected.

Conclusion

Intravitreal implantation of the biodegradable CsA-PGLC DDS may effectively reduce the intraocular inflammation in rabbits with no toxicity, which provides a potentially safe and convenient approach for the treatment of chronic uveitis.
Literatur
1.
Zurück zum Zitat Cai Q, Bei J, Wang S (2000) Synthesis and degradation of a tri-component copolymer derived from glycolide, L-lactide, and epsilon-caprolactone. J Biomater Sci Polym Ed 11:273–288CrossRefPubMed Cai Q, Bei J, Wang S (2000) Synthesis and degradation of a tri-component copolymer derived from glycolide, L-lactide, and epsilon-caprolactone. J Biomater Sci Polym Ed 11:273–288CrossRefPubMed
2.
Zurück zum Zitat Gilger BC, Malok E, Stewart T, Horohov D, Ashton P, Smith T, Jaffe GJ, Allen JB (2000) Effect of an intravitreal cyclosporine implant on experimental uveitis in horses. Vet Immunol Immunopathol 76:239–255CrossRefPubMed Gilger BC, Malok E, Stewart T, Horohov D, Ashton P, Smith T, Jaffe GJ, Allen JB (2000) Effect of an intravitreal cyclosporine implant on experimental uveitis in horses. Vet Immunol Immunopathol 76:239–255CrossRefPubMed
3.
Zurück zum Zitat Jaffe GJ, Yang CS, Wang XC, Cousins SW, Gallemore RP, Ashton P (1998) Intravitreal sustained-release cyclosporine in the treatment of experimental uveitis. Ophthalmology 105:46–56PubMedCrossRef Jaffe GJ, Yang CS, Wang XC, Cousins SW, Gallemore RP, Ashton P (1998) Intravitreal sustained-release cyclosporine in the treatment of experimental uveitis. Ophthalmology 105:46–56PubMedCrossRef
4.
Zurück zum Zitat Kulkarni P (2001) Review: uveitis and immunosuppressive drugs. J Ocular Pharmacol Ther 17:181–187CrossRef Kulkarni P (2001) Review: uveitis and immunosuppressive drugs. J Ocular Pharmacol Ther 17:181–187CrossRef
5.
Zurück zum Zitat Lafferty KJ, Borel JF, Hodgkin P (1983) Cyclosporin A (CsA): models for the mechanism of action. Transplant Proc 15:2242–2247 Lafferty KJ, Borel JF, Hodgkin P (1983) Cyclosporin A (CsA): models for the mechanism of action. Transplant Proc 15:2242–2247
6.
Zurück zum Zitat Liu C, Sun R (1999) Experiment design and statistics application for drug evaluation. Military Medical Science Academy, Beijing, p 19 Liu C, Sun R (1999) Experiment design and statistics application for drug evaluation. Military Medical Science Academy, Beijing, p 19
7.
Zurück zum Zitat Nussenblatt RB, Dinning WJ, Fujikawa LS, Chan CC, Palestine AG (1985) Local cyclosporine therapy for experimental autoimmune uveitis in rats. Arch Ophthalmol 103:1559–1562PubMed Nussenblatt RB, Dinning WJ, Fujikawa LS, Chan CC, Palestine AG (1985) Local cyclosporine therapy for experimental autoimmune uveitis in rats. Arch Ophthalmol 103:1559–1562PubMed
8.
Zurück zum Zitat Shi W, Xie L, Wang S (2002) Prolongation of corneal allograft survival in mice with a cyclosporine drug delivery system implant. Chin J Ophthalmol 38:502–505 Shi W, Xie L, Wang S (2002) Prolongation of corneal allograft survival in mice with a cyclosporine drug delivery system implant. Chin J Ophthalmol 38:502–505
9.
Zurück zum Zitat Sullu Y, Oge I, Erkan D, Ariturk N, Mohajeri F (1998) Cyclosporin-A therapy in severe uveitis of Behcet’s disease. Acta Ophthalmol Scand 76:96–99PubMedCrossRef Sullu Y, Oge I, Erkan D, Ariturk N, Mohajeri F (1998) Cyclosporin-A therapy in severe uveitis of Behcet’s disease. Acta Ophthalmol Scand 76:96–99PubMedCrossRef
10.
Zurück zum Zitat Vitale AT, Rodriguez A, Foster CS (1996) Low-dose cyclosporin A therapy in treating chronic, noninfectious uveitis. Ophthalmology 103:365–374PubMed Vitale AT, Rodriguez A, Foster CS (1996) Low-dose cyclosporin A therapy in treating chronic, noninfectious uveitis. Ophthalmology 103:365–374PubMed
11.
Zurück zum Zitat Yang P, Li S (1998) Uveitis. People's Medical Publishing, Beijing, pp 64–186 Yang P, Li S (1998) Uveitis. People's Medical Publishing, Beijing, pp 64–186
Metadaten
Titel
Intravitreal implantation of the biodegradable cyclosporin A drug delivery system for experimental chronic uveitis
verfasst von
Xiaoguang Dong
Weiyun Shi
Gongqiang Yuan
Lixin Xie
Shenguo Wang
Ping Lin
Publikationsdatum
01.04.2006
Verlag
Springer-Verlag
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 4/2006
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-005-0109-1

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