کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5550940 1557304 2016 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
High systemic availability of core-crosslinked polymeric micelles after subcutaneous administration
ترجمه فارسی عنوان
در دسترس بودن سیستمیک بالا از میسلهای پلیمری متصل به هسته ای پس از تزریق زیر جلدی
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
چکیده انگلیسی

Covalent entrapment of drug molecules within core-crosslinked polymeric micelles (CCPM) represents an attractive approach to improve their therapeutic index. As an alternative to the most commonly employed intravenous (i.v.) route, subcutaneous (s.c.) administration offers the possibility of self-administration and thereby may reduce healthcare costs. The aim of this work was to assess the pharmacokinetic profile and systemic availability of drug-containing CCPM following s.c. injection. We here derivatised dexamethasone (DMS) with three different linkers, which enabled covalent attachment of this drug to the core of CCPM. The obtained DMS-containing CCPM exhibited varying drug release kinetics in vitro. Remarkably, a single dose of DMS-containing CCPM resulted in high systemic availability of about 30% following s.c. injection into the flank of healthy mice, as evidenced by an AUC between 26-37% relative to the AUC attained following i.v. injection. Although different linkers resulted in moderate variations in pharmacokinetic parameters, the overall pharmacokinetic profiles of these i.v. or s.c. administered nanomedicines were not substantially different. Next to DMS, we covalently attached paclitaxel (PTX) to the core of CCPM. Similarly, a single s.c. dose of PTX-containing CCPM resulted in high systemic availability of about 40% compared to i.v. injection and PTX (entrapped plus released) was detected in the blood for at least 3 days. Importantly, the systemic availability of s.c. administered drug-containing CCPM is substantially higher than that of other nanoformulations as reported in the literature (e.g. 3% in rodents). These results demonstrate that s.c. administration is a promising route to attain high systemic availability of CCPM, enabling a potentially more patient-friendly and cost-effective treatment approach than the i.v. route.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 514, Issue 1, 30 November 2016, Pages 112-120
نویسندگان
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