树枝状大分子的生物相容性和毒性。
Dendrimer biocompatibility and toxicity.
作者信息
Duncan Ruth, Izzo Lorella
机构信息
Centre for Polymer Therapeutics, Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3XF, UK.
出版信息
Adv Drug Deliv Rev. 2005 Dec 14;57(15):2215-37. doi: 10.1016/j.addr.2005.09.019. Epub 2005 Nov 16.
The field of biomedical dendrimers is still in its infancy, but the explosion of interest in dendrimers and dendronised polymers as inherently active therapeutic agents, as vectors for targeted delivery of drugs, peptides and oligonucleotides, and as permeability enhancers able to promote oral and transdermal drug delivery makes it timely to review current knowledge regarding the toxicology of these dendrimer chemistries (currently under development for biomedical applications). Clinical experience with polymeric excipients, plasma expanders, and most recently the development of more 'classical polymer'-derived therapeutics can be used to guide development of "safe" dendritic polymers. Moreover, in future it will only ever be possible to designate a dendrimer as "safe" when related to a specific application. The so far limited clinical experience using dendrimers make it impossible to designate any particular chemistry intrinsically "safe" or "toxic". Although there is widespread concern as to the safety of nano-sized particles, preclinical and clinical experience gained during the development of polymeric excipients, biomedical polymers and polymer therapeutics shows that judicious development of dendrimer chemistry for each specific application will ensure development of safe and important materials for biomedical and pharmaceutical use.
生物医学树枝状大分子领域仍处于起步阶段,但人们对树枝状大分子和树枝状聚合物作为固有活性治疗剂、药物、肽和寡核苷酸靶向递送载体以及能够促进口服和透皮给药的渗透增强剂的兴趣激增,因此有必要及时回顾有关这些树枝状大分子化学(目前正在开发用于生物医学应用)毒理学的现有知识。聚合物辅料、血浆扩容剂的临床经验,以及最近更多“经典聚合物”衍生疗法的发展,可用于指导“安全”树枝状聚合物的开发。此外,未来只有在与特定应用相关时,才有可能将树枝状大分子指定为“安全”。目前使用树枝状大分子的临床经验有限,因此无法将任何特定化学物质本质上指定为“安全”或“有毒”。尽管人们普遍关注纳米级颗粒的安全性,但在聚合物辅料、生物医学聚合物和聚合物疗法开发过程中获得的临床前和临床经验表明,针对每种特定应用明智地开发树枝状大分子化学将确保开发出用于生物医学和制药用途的安全且重要的材料。