使用阿糖胞苷的多功能柠檬酸树状大分子的体外细胞毒性、体内药代动力学研究和组织分布研究

K. Reddy, B Narasimha Rao, KB Chandra Sekhar
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摘要

树状大分子被认为是新兴的聚合物结构,以其明确的分子量、多分散性、均匀性和高表面功能而闻名。这些纳米结构能够通过共价键和主客体相互作用在其内部或外部封装低分子量药物部分。此外,大的表面体积使研究人员将树状大分子应用于生物医学和治疗领域。尽管有大量的应用,但由于其产生的细胞毒性,有时其使用受到限制。考虑到这一点,目前的研究重点是柠檬酸树状大分子的合成和聚乙二醇化。聚乙二醇化是一种将聚乙二醇偶联到树状大分子上的行为,它完全消除了与树状大分子相关的毒性问题,并使它们具有生物相容性。阿糖胞苷被装载在树突结构中,以特异性靶向肿瘤细胞。树状大分子是通过结合某些在肿瘤环境中被切割的试剂而产生肿瘤特异性的。研究了合成树状大分子对急性细胞毒性、组织分布和药代动力学参数的影响。
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In vitro cytotoxicity, in vivo pharmacokinetic studies and tissue distribution studies of multifunctional citric acid dendrimers using the drug Cytarabine
Dendrimers are considered the emerging polymeric architectures, known for their well defined molecular-weight, polydispersity, uniformity and high-surface functionality. These nano-architectures are capable of encapsulating low-high molecular-weight drug moieties in their interior or exterior through covalent bonding and host-guest interactions. Further, large surface volume made researchers to implicate dendrimers in biomedical and therapeutic applications. Regardless of the massive applications, sometimes its use is limited because of the cytotoxicity produced.  Considering this, the present research is focused on the synthesis and PEGylation of citric acid dendrimers. PEGylation is an act of conjugating polyethylene glycol to dendrimers that completely eliminates the toxicity issues associated with dendrimers and render them biocompatible. Cytarabine was loaded in the dendritic architecture to target specifically the tumor cells. Dendrimers are made tumor specific by incorporating certain agents that get cleaved in tumor environment. Synthesized dendrimers were studied for its effect on acute cytotoxicity, tissue-distributions and pharmacokinetic parameters.
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