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Kemp et al. Page 8 The effects of free DAPHP, Au-DAPHP and Ag-DAPHP on carrageenan-induced paw edema in rats as compared to Indomethacin were evaluated. Significant inhibition of carrageenan- induced paw edema was shown for Au-glucose or Ag-glucose, Au-HA or Ag-HA versus heparin (Figure 9A and B). In contrast, Au-DAPHP and Ag-DAPHP nanoparticles administered locally in the paw did not exhibit any systemic effect on aPTT as compared to locally administered heparin (Figure 9C). Data indicated significant inhibition of carrageenan- induced paw edema in rats by Au-glucose, Ag-glucose, Au-HA, Ag-HA, heparin, Au-DAPHP and Ag-DAPHP, without any systemic effects on hemostasis as compared to heparin suggesting the potential for local inhibition of inflammation without systemic adverse effect using Au-heparin or Ag-heparin as compare to free heparin. Conclusions The current study demonstrates that Au and Ag nanoparticle composites can be synthesized and stabilized with both heparin and hyaluronan. The nanocomposites are much more stable at physiological electrolyte concentrations than naked nanoparticles, because the heparin bound to the particles provides electrostatic repulsion from other particles. Furthermore, the current study also demonstrates in vivo and in vitro biological activity. Heparin bound to both Au and Ag nanoparticles still retains its anticoagulant activity. Heparin present on the surface increases the biocompatibility of these nanoparticles. These derivatized particles can be further modified and used as nano-carriers in vivo with reduced risk of coagulation and rejection from the immune system. This studied also showed that these particles can provide localization for anti-inflammatory applications. Localization can be important to deliver a more prolonged effect of these nanocomposites; while other drugs can rapidly diffuse into the body, reducing their activity over time. These nanocomposites maybe useful in a wide variety of biological and biomedical applications that take advantage of the biological activities of heparin and hyaluronan, as well as the unique physical attributes of Au and Ag core nanoparticles. Supplementary Material Refer to Web version on PubMed Central for supplementary material. Acknowledgments This work was supported by grants from the National Institutes of Health (HL62244 to RJL), (The Pharmaceutical Research Institute to SM) and the National Science Foundation (III-CXT: 0713517 and CRI:IAD: 0709099 (IIS0713517) to RJL). References 1. O’Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL. Cancer Lett (Amsterdam, Neth) 2004;209:171– 176. 2. Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Rivera B, Price RE, Hazle JD, Halas NJ, West JL. Proc Natl Acad Sci U S A 2003;100:13549–13554. [PubMed: 14597719] 3. Huang X, El-Sayed IH, Qian W, El-Sayed MA. J Am Chem Soc 2006;128:2115–2120. [PubMed: 16464114] 4. Cognet L, Tardin C, Boyer D, Choquet D, Tamarat P, Lounis B. Proc Natl Acad Sci U S A 2003;100:11350–11355. [PubMed: 13679586] 5. Skirtach AG, Dejugnat C, Braun D, Susha AS, Rogach AL, Parak WJ, Moehwald H, Sukhorukov GB. Nano Lett 2005;5:1371–1377. [PubMed: 16178241] 6. Li J, Wang X, Wang C, Chen B, Dai Y, Zhang R, Song M, Lv G, Fu D. ChemMedChem 2007;2:374– 378. [PubMed: 17206735] 7. Shrivas K, Wu HF. Anal Chem (Washington, DC, U S) 2008;80:2583–2589. 8. Lee JS, Ulmann PA, Han MS, Mirkin CA. Nano Lett 2008;8:529–533. [PubMed: 18205426] Biomacromolecules. Author manuscript; available in PMC 2010 March 9. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptPDF Image | Gold and Silver Nanoparticles Stabilized Glycosaminoglycans
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