An anionic amphiphilic dendrimer is reported that possesses increased cytotoxicological potency against prokaryotic cells compared to eukaryotic cells. The half maximal effective concentration (EC 50 ) for the dendrimer against Bacillus subtilis, a Gram-positive bacterial strain, was measured to be 4.1×10 −5 M, while that against human umbilical vein endothelial cells (HUVEC) was more than 36x greater at a value of 1.5×10 −3 M. EC 50 ratios for two commercial amphiphiles, sodium dodecyl sulfate (SDS) and Triton X-100, in addition to a similar synthesized dendritic structure were at most only 3.8x greater. Furthermore, the observed EC 50 values appear to be correlated to the critical aggregation constant (CAC) in solution suggesting a mechanism of action for these anionic amphiphilic dendrimers related to their supramolecular structures.Dendritic macromolecules, due to their structure, unique properties, and precise compositions, are of significant interest 1 and are finding uses in an ever-increasing number of medical applications. 2 This is especially evident in the drug delivery area where the dendritic structure enables the attachment of a multitude of drugs or targeting moieties as well as the opportunity to control pharmacokinetics through alterations in generation number. 3 Our interest lies in the synthesis and evaluation of dendritic macromolecules composed of building blocks that are natural metabolites or known to be biocompatible for ocular tissue repair, 4 cartilage tissue engineering, 5 and drug delivery. 6 In an ongoing effort to expand the biomedical applications of dendrimers and our understandings of the resulting structure-activity relationships, we are investigating anionic dendritic macromolecules as antibacterial agents. Herein, we report the antibacterial activity of an anionic amphiphilic dendrimer and the striking selectivity in its E-mail: mgrin@bu.edu. There is a significant global need for new antibacterials and alternative mechanisms of action given the rise in resistance among bacteria. 7 Of the various known antibacterial agent classes, amphiphilic compounds act through perturbation and disruption of the prokaryotic membrane. 8 We hypothesized that amphiphilic anionic dendrimers may exhibit antibacterial activity with minimal eukaryotic cell cytotoxicity, since dendrimers with terminal anionic charges are generally non-cytotoxic and have low toxicity in zebrafish whole animal development studies. 9 On the other hand, cationic dendrimers, some of which have antibacterial properties if the positive charge is properly shielded, 10 have repeatedly shown cytotoxicity against a variety of eukaryotic cell lines. 3e,11 In addition, there are many reports of linear polycationic agents but only a few descriptions of linear polyanionic antibacterial agents (e.g., sulfonated polystyrene). 12 Consequently, we synthesized a series of surface-block anionic amphiphilic dendrimers composed of succinic acid, glycerol, and myristic acid possessing various numbers of acid and alkyl functionali...

Research on dendrimers continues to expand as further advances in synthetic methodology and characterization techniques translate to additional applications. Recently, dendritic polymers composed of the natural metabolites glycerol and succinic acid were synthesized, functionalized, and evaluated as new medical materials. The design and synthesis of poly(glycerol-succinic acid) dendritic polymers are discussed, including comparing and contrasting the convergent versus the divergent methodologies for preparing such macromolecules. Finally, a photocrosslinkable dendritic macromolecule was prepared and successfully used to close linear corneal lacerations as well as to secure LASIK flaps.