Dendrimer biocompatibility and toxicity.
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.
Duncan
Ruth
R
Centre for Polymer Therapeutics, Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3XF, UK. DuncanR@cf.ac.uk
Izzo
Lorella
L
D000818:Animals; D001672:Biocompatible Materials; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D011073:Polyamines / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution
D001672:Biocompatible Materials; D018925:Chemokines; D016207:Cytokines; D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines