Subacute toxicity of all-trans-retinoic acid loaded biodegradable microspheres in rats
- Authors
- Choi, Yongdoo; Lee, Chulkyu; Park, Kyeongsoon; Kim, Sang Yoon; Kim, Sun Hee; Han, Shin; Kim, Sung Hyun; Byun, Youngro
- Issue Date
- Jul-2003
- Publisher
- WILEY-LISS
- Keywords
- all-traps-retinoic acid; PDLLA; microsphere; subacute toxicity
- Citation
- DRUG DEVELOPMENT RESEARCH, v.59, no.3, pp 326 - 332
- Pages
- 7
- Journal Title
- DRUG DEVELOPMENT RESEARCH
- Volume
- 59
- Number
- 3
- Start Page
- 326
- End Page
- 332
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/50323
- DOI
- 10.1002/ddr.10283
- ISSN
- 1098-2299
0272-4391
- Abstract
- Biodegradable microspheres containing all-traps-retinoic acid (atRA) were prepared previously to enhance the clinical efficacy of atRA for chemoprevention. In this study, subacute toxicity of atRA in sustained release was evaluated after subcutaneous administration of 0, 25, 50, and 100 mg atRA/kg of atRA-loaded microspheres. After the subcutaneous injection of atRA-loaded microspheres, the atRA concentration in plasma was maintained in the range of 3.5-25 ng/ml for 2-3 weeks. When 100 mg atRA/kg was administered, the atRA concentration in plasma was maintained at levels greater than 10 ng/ml and severe toxic effects were observed. When the dose of 50 mg atRA/kg was administered, the plasma concentration of atRA was maintained below 10 ng/ml over 3 weeks and only mild signs of toxicity were observed. Therefore, it was concluded that the dosage of atRA-loaded microspheres should be less than 50 mg atRA/kg for chemopreventive applications against carcinogenesis. Considering recovery from intoxication, the optimum interval for repeated injection of the microspheres was suggested to be over 4 weeks. In addition, it was found that the atRA concentration in plasma should be controlled below 10 ng/ml to minimize toxic effects of atRA. (C) 2003 Wiley-Liss, Inc.
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