Novel Self-Patented Gold Nanoparticles for Antimicrobial Applications

J. Payne, R. Dakshinamurthy
Austin Peay State University,
United States

Keywords: antibacterial

Summary:

The development of antibiotic resistance in bacteria is a growing problem that is limiting our ability of effectively treat infectious diseases around the world. While significant efforts are needed to identify new antimicrobial targets and compounds, these are lengthy processes that will take many years to move from target identification to an FDA-approved clinical drug. A secondary strategy that can support these drug discovery programs is to improve the efficacy of existing antibiotics. The advantage of this secondary strategy is that improving existing antibiotics should result in therapies that can move to the clinic much quicker than the development of novel antimicrobials. Nanoscale materials bring new possibilities into medicinal chemistry. Due to their chemical stability, ease of surface functionalization and relative safety, gold nanoparticles (GNPs) have been used for several years for cancer drug delivery [1,2]. Furthermore, GNPs have also been investigated for use to fight bacterial infections. So it is important for the continued investigation of new synthesis and drug combinations to identify the best GNP-antibiotic approaches for medical use. Typically conjugation to GNPs is typically done using amino acids, glutathione, or polyethylene glycol as functionalizing agents (i.e., linkers) [4,5]. The addition of these linkers can reduce the efficacy of conjugated antibiotics and/or interfere with the stability of the drugs. Furthermore, many conjugation chemistries use synthesis processes that are dependent on organic substances and external sources (such as laser pulses) for synthesis and/or the activation of GNPs that are quite labor intensive and not environmentally friendly [4-7]. To overcome these problems, we have developed a simple, environmentally friendly process to rapidly generate substrate-capped GNPs that require no linkers (U.S. Patent No. 8,257,670) [8-13]. Importantly, this process uses an aqueous medium, has no purification steps, and has tunable size distribution (i.e., can be manipulated to generate different size GNPs). We have shown that this process can be used to safely and rapidly generate antibiotic-capped GNPs (Ab-GNPs) that retain antimicrobial efficacy. Conjugating antibiotics to GNPs has the potential to increase the efficacy of antibiotics by increasing the stability or local concentration of the antibiotic at the site of infection [18,19]. However, the direct contribution of the antimicrobial characteristics of GNPs may also increase the efficacy of the Ab-GNP conjugate. In this context, the current project deals with the antimicrobial aspects of GNPs, in addition to drug delivery capabilities, to develop an innovative and novel drug platform to increase the efficacy of FDA approved antibiotics. We anticipate that our Ab-GNPs conjugated drug platforms, which will have two independent antimicrobial properties, GNP- and antibiotic-specific, will have greater efficacy against antibiotic resistant strains (due to increased local concentration of antibiotic and susceptibility to GNP-killing). Furthermore, this innovative drug platform has the potential to slow the development of antibiotic resistance in susceptible strains, as bacteria would have to develop resistance to both the antibiotic and the GNP in order to survive. Results of these studies not only provide us a novel synthesis method but also yield efficient drug delivery.