Silver Nanoparticles in Therapeutics: Development of an Antimicrobial Gel Formulation for Topical Use

• Published in: Molecular pharmaceutics 2009-10, Vol.6 (5), p.1388-1401
• Main Authors: Jain, Jaya, Arora, Sumit, Rajwade, Jyutika M, Omray, Pratibha, Khandelwal, Sanjeev, Paknikar, Kishore M
• Format: Article
• Language: English
• Subjects: Administration, Topical; Animals; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - toxicity; Antioxidants - metabolism; Aspergillus niger; Candida albicans; Cell Survival - drug effects; Gels; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Hep G2 Cells; Humans; Matrix Metalloproteinase Inhibitors; Metal Nanoparticles - administration & dosage; Metal Nanoparticles - toxicity; Metal Nanoparticles - ultrastructure; Microbial Sensitivity Tests; Microscopy, Electron, Transmission; Nanotechnology; Pseudomonas aeruginosa; Rats; Rats, Sprague-Dawley; Silver - administration & dosage; Silver - toxicity; Skin - drug effects; Staphylococcus
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp900056g

Silver is an effective antimicrobial agent with low toxicity, which is important especially in the treatment of burn wounds where transient bacteremia is prevalent and its fast control is essential. Drugs releasing silver in ionic forms are known to get neutralized in biological fluids and upon long-term use may cause cosmetic abnormality, e.g., argyria and delayed wound healing. Given its broad spectrum activity, efficacy and lower costs, the search for newer and superior silver based antimicrobial agents is necessary. Among the various options available, silver nanoparticles have been the focus of increasing interest and are being heralded as an excellent candidate for therapeutic purposes. This report gives an account of our work on development of an antimicrobial gel formulation containing silver nanoparticles (SNP) in the size range of 7−20 nm synthesized by a proprietary biostabilization process. The typical minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against standard reference cultures as well as multidrug-resistant organisms were 0.78−6.25 μg/mL and 12.5 μg/mL, respectively. Gram-negative bacteria were killed more effectively (3 log10 decrease in 5−9 h) than Gram-positive bacteria (3 log10 decrease in 12 h). SNP also exhibited good antifungal activity (50% inhibition at 75 μg/mL with antifungal index 55.5% against Aspergillus niger and MIC of 25 μg/mL against Candida albicans). When the interaction of SNP with commonly used antibiotics was investigated, the observed effects were synergistic (ceftazidime), additive (streptomycin, kanamycin, ampiclox, polymyxin B) and antagonistic (chloramphenicol). Interestingly, SNP exhibited good anti-inflammatory properties as indicated by concentration-dependent inhibition of marker enzymes (matrix metalloproteinase 2 and 9). The post agent effect (a parameter measuring the length of time for which bacterial growth remains suppressed following brief exposure to the antimicrobial agent) varied with the type of organism (e.g., 10.5 h for P. aeruginosa, 1.3 h for Staphylococcus sp. and 1.6 h for Candida albicans) indicating that dose regimen of the SNP formulation should ensure sustained release of the drug. To meet this requirement, a gel formulation containing SNP (S-gel) was prepared. The antibacterial spectrum of S-gel was found to be comparable to that of a commercial formulation of silver sulfadiazine, albeit at a 30-fold less silver concentration. As part of toxicity s