Biocompatibility and Toxicity of Dendrimers
The terms of toxicity and biocompatibility of dendrimers are closely related. For biomedical applications, dendrimers should be devoid of toxicity and immunogenicity. The first concept—“toxicity”—is mainly applied by pharmacompanies for description of adv
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Biocompatibility and Toxicity of Dendrimers
Closely related terms of toxicity and biocompatibility of dendrimers are important for biomedical applications [1, 3–5, 7, 24, 25, 27, 28, 31, 35]. Dendrimers should be devoid of toxicity and immunogenicity. The first concept—toxicity—is mainly applied by pharmacompanies for description of adverse effects to cells, organs, or patients. The second concept—“biocompatibility”—belongs to the field of biomedical materials as an extent of their compatibility with the studied system. One can say that biocompatibility and toxicity are inversely proportional, i.e., the more biocompatible the less toxic it is. Since 1986, biocompatibility is defined as the capability of a material to act with a proper host response in a specific application [7, 22, 25, 33]. Therefore, a biocompatibility of material can be described only if the precise context of material usage is known. Without knowledge of the exact usage of dendrimer, any chemistry cannot be defined as nontoxic or biocompatible. Clinical experience with dendrimers is still in its infancy; therefore, it is impossible to specify any chemistry insistingly biocompatible or toxic [7, 25]. The negative charge of most cell membranes interacts with amino surface groups of dendrimers. These electrostatic interactions significantly influence the stability and permeability of membranes [9, 12, 22, 25, 30]. The dendrimer–membrane interactions are also responsible for their high cellular uptake by endocytosis. However, G3 and higher generations of amino terminated dendrimers have a destructive interaction with the membrane, which causes cellular lysis and high cytotoxicity. Obviously, negatively charged dendrimers repulse with negatively charged membranes and therefore do not have generation-dependent cytotoxicity. For non-charged dendrimers, their cytotoxicity is influenced by polarity of surface groups. For instance, polar groups like PEG do not induce a toxic behavior. On the contrary, nonpolar groups like lipids could invade the membranes by hydrophobic interactions. This could result in dendrimer toxicity. Lipids can act as immunostimulators and positively influence the cells. The particle size is a key player for biodistribution, clearance, and toxicity of dendrimers. The role of nanoparticles is summarized in Chap. 12.
ˇ J. Sebest´ ık et al., Biomedical Applications of Peptide-, Glyco- and Glycopeptide Dendrimers, and Analogous Dendrimeric Structures, DOI 10.1007/978-3-7091-1206-9 11, © Springer-Verlag Wien 2012
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11 Biocompatibility and Toxicity of Dendrimers
Inherent toxicity of PAMAM dendrimers, as well as their reticuloendothelial system uptake, and hemolysis restrict their clinical applications in drug delivery [35]. Due to positive charge and the surface size, there is a correlation between toxicological response of PAMAM dendrimers and the dendrimer generation [20, 21]. The higher the particle surface area the higher is the toxic response [25]. Interestingly, the surface modifications can modulate dendrimer toxicity
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