Biological Assessment of Triazine Dendrimer: Toxicological Profiles, Solution Behavior, Biodistribution, Drug Release and Efficacy in a PEGylated, Paclitaxel Construct
| العنوان: | Biological Assessment of Triazine Dendrimer: Toxicological Profiles, Solution Behavior, Biodistribution, Drug Release and Efficacy in a PEGylated, Paclitaxel Construct |
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| المؤلفون: | Jiwen Zheng, Jongdoo Lim, Pavan P. Adiseshaiah, Jeffrey D. Clogston, Xiankai Sun, Anil K. Patri, Stephan T. Stern, Marina A. Dobrovolskaia, Eric E. Simanek, Su-Tang Lo |
| المصدر: | Molecular Pharmaceutics. 7:993-1006 |
| بيانات النشر: | American Chemical Society (ACS), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Pegylated Paclitaxel, Biodistribution, Chemistry, Pharmaceutical Science, Pharmacology, Orders of magnitude (mass), In vitro, chemistry.chemical_compound, Paclitaxel, In vivo, Dendrimer, Drug Discovery, Molecular Medicine, Cytotoxicity |
| الوصف: | The physicochemical characteristics, in vitro properties, and in vivo toxicity and efficacy of a third generation triazine dendrimer bearing approximately nine 2 kDa polyethylene glycol chains and twelve ester linked paclitaxel groups are reported. The hydrodynamic diameter of the neutral construct varies slightly with aqueous solvent ranging from 15.6 to 19.4 nm. Mass spectrometry and light scattering suggest radically different molecular weights with the former approximately 40 kDa mass consistent with expectation, and the latter 400 kDa mass consistent with a decameric structure and the observed hydrodynamic radii. HPLC can be used to assess purity as well as paclitaxel release, which is insignificant in organic solvents or aqueous solutions at neutral and low pH. Paclitaxel release occurs in vitro in human, rat, and mouse plasma and is nonlinear, ranging from 7 to 20% cumulative release over a 48 h incubation period. The construct is 2-3 orders of magnitude less toxic than Taxol by weight in human hepatocarcinoma (Hep G2), porcine renal proximal tubule (LLC-PK1), and human colon carcinoma (LS174T) cells, but shows similar cytotoxicity to Abraxane in LS174T cells. Both Taxol and the construct appear to induce caspase 3-dependent apoptosis. The construct shows a low level of endotoxin, is not hemolytic and does not induce platelet aggregation in vitro, but does appear to reduce collagen-induced platelet aggregation in vitro. Furthermore, the dendrimer formulation slightly activates the complement system in vitro due most likely to the presence of trace amounts ( |
| تدمد: | 1543-8392 1543-8384 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::8bf70fce1923894dd144250465cded40Test https://doi.org/10.1021/mp100104xTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........8bf70fce1923894dd144250465cded40 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15438392 15438384 |
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