کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8414560 | 1545351 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Charge affects the oral toxicity of poly(amidoamine) dendrimers
ترجمه فارسی عنوان
شارژ سمیت خوراکی دندریمر های پلی (آمیدامین) را تحت تاثیر قرار می دهد
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیوتکنولوژی یا زیستفناوری
چکیده انگلیسی
Poly(amidoamine) (PAMAM) dendrimers have been evaluated for the influence of surface functionality and size on the epithelial barrier of the gut with the goal of identifying safe carriers that can be used for oral drug delivery. Limited studies are conducted to date, however, to assess the toxicity of PAMAM dendrimers in vivo when administered by the oral route. The goal of this research was to conduct an oral acute toxicity study of PAMAM dendrimers as a function of size and charge in immune competent CD-1 mice. Maximum tolerated doses (MTD) of PAMAM dendrimers as a function of size and surface functionality were established and clinical signs of toxicity monitored. Results demonstrate that positively charged dendrimers caused more toxicity, whereas their anionic counterparts were tolerated at ten times higher doses. Severe signs of toxicity observed for large (G7) cationic amine- or hydroxyl-terminated dendrimers include hemobilia and spleenomegaly. The MTD for these dendrimers ranged from 30Â mg/kg to 200Â mg/kg. Anionic G6.5 or smaller molecular weight carboxyl-, amine-, or hydroxyl-terminated dendrimers (G3.5-COOH, G4-NH2, G4-OH) on the other hand were tolerated at doses of up to 500Â mg/kg (300Â mg/kg in some cases) with minimal or no signs of toxicity. Establishing the MTD of orally delivered PAMAM dendrimers and the influence of surface functionality and size on toxicity aids in the rational design of PAMAM-drug conjugates for oral drug delivery applications.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 84, Issue 2, June 2013, Pages 330-334
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 84, Issue 2, June 2013, Pages 330-334
نویسندگان
Giridhar Thiagarajan, Khaled Greish, Hamidreza Ghandehari,