Dendrimer−Silver Complexes and Nanocomposites as Antimicrobial Agents

Silver complexes of poly(amidoamine) (PAMAM) dendrimers as well as different {silver−PAMAM} dendrimer nanocomposite solutions have been tested in vitro against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli bacteria, using the standard agar overlay method. Both PAMAM silver salts and nanocomposites displayed considerable antimicrobial activity without the loss of solubility and activity, even in the presence of sulfate or chloride ions. Introduction. The usefulness of silver as an antimicrobial agent has been known for a long time. It is an effective agent with low toxicity, which is especially important in the topical antibacterial treatment of burn wounds, where transient bacteremia is commonly cited.1 Silver sulfonamides, particularly silver sulfadiazine2 (AgSD), have been used as the standard treatment for burns over the past two decades, either alone or in combination with other antibiotics,3 cerium,4 and zinc compounds.5 It was suggested that the basic function of the almost insoluble AgSD may be the slow release of silver into the superficial wound environment.6 Silver chloride was assumed to form at the burn wound, and the absorption of silver was believed to be negligible.7 In accordance with this assumption, it was found that serum and tissue silver levels with 10% silver nitrate used in burns produced no difference from that of 1% silver sulfadiazine cream.8 However, sulfonamide-resistant organisms have been reported as a frequent consequence of the clinical use of sulfadiazine silver.9 It was also shown that the sulfadiazine component is not necessary for in vitro sensitivity, and the use of sulfadiazine silver in every case can, therefore, lead to the selection of organisms that are resistant not only to sulfonamides but also to antibiotics of clinical consequence.10 In a new approach, silver nylon dressings were tested on Pseudomonas aeruginosa-infected burn wounds. Silver nylon was therapeutic when used as a surface anode or cathode, and, to some extent, even without any applied weak direct current. This result indicated that silver nylon dressings may be a valuable antimicrobial burn wound covering device.11 Despite major advances in burn wound management and other supportive care regimens, infection remains the leading cause of morbidity in the thermally injured patient,12 and the search for different treatments and new ideas is continuing. The application of silver-binding membranes has recently been suggested to further reduce the likelihood of silver toxicity to retard the movement of silver ions and minimize silver absorption at a healing wound.13,14 Dendrimers15-19 are symmetrical and spherical macromolecules, comprising a relatively dense shell composed of a core, branching sites, and terminal groups that usually form a well-defined surface. Their interior may be similar or very different from the surface of the molecule. Chemical and/or physical properties, such as reactivity, complex or salt formation, hydrophilicity, and so forth can be varied and optimized. Poly(amidoamine) PAMAM dendrimers are obtained by the iterative branching of â-alanine repeat units. Due to their biofriendly nature20-22 and unique carrier properties, they show promise to outperform other polymeric materials14 for medical applications. Diffusion of dendrimers through membranes is the function of generation (due to their spherical and monomodal character), and appropriately selected membranes may retain dendrimer hosts with 100% selectivity. PAMAMs are also stable and soluble in water. Dendrimers are now recognized as monodispersed nanoreactors possessing architectures and ligand sites that allow * To whom correspondence should be addressed. University of Michigan Center for Biologic Nanotechnology, University of Michigan, Department of Internal Medicine, 4010 Kresge Research Building-II, 200 Zina Pitcher Pl., Ann Arbor, MI 48109-0533. Phone: (734) 615-0623. Fax: (734) 6150621. E-mail: [email protected]. † AMSRL-WM-MA, US Army Research Laboratory, APG, MD, 21005. ‡ MCMR-USM-M, US Army Institute of Surgical Research, Fort Sam Houston, Texas 78234-6315. NANO LETTERS 2001 Vol. 1, No. 1 18-21 10.1021/nl005502p CCC: $20.00 © 2001 American Chemical Society Published on Web 11/28/2000 Report Documentation Page Form Approved