Silver Ion ReleASE FROM A SILVER Fiber Hydrogel Wound Dressing

A.
1 Fluder ,

LB-27
*Corresponding author Joseph B. Laudano (jlaudano@alliqua.com) Vice President, Medical Affairs, Alliqua, Inc. 850 3rd Avenue, New York, New York 10022
Presenting

J.

2* Laudano ,

J.

3 Smiell ,

S.

4 Snyder ,

P.

5 1 Forman AquaMed

Technologies Inc.,

2Alliqua

Inc.,

3JMS

Clinical LLC,

4Advanced

Clinical Perspectives LLC,

5Center

for Wound Healing Inc.

author

abstract
The effectiveness of silver fiber hydrogel wound dressings is based on the antimicrobial effect of the silver ions (Ag+) on bacterial or fungal 1 pathogens absorbed onto the dressing from the wound. Ag+ released from the dressing at a concentration of >1ppm is considered bactericidal.2 The delivery of Ag+ from a silver-coated nylon fiber hydrogel wound dressing* was investigated. First, 3 samples of silver-hydrogel dressing were placed in purified water (1:100 by weight), then placed in a 37C oven (to simulate body temperature) for 30 minutes, after which extracts were obtained and tested for Ag+. After 30 minutes, Ag+ concentration was <0.1 ppm. Next, the release of Ag+ was assessed over 8 days. Under similar conditions, 3 samples were placed in the oven for 24 hours, after which, the samples were removed and extracts obtained. The samples were placed in fresh purified water and returned to the oven for another 24 hours. This process was repeated with fresh purified water every 24 hours through Day 8. On Day 9, extracts were again obtained and tested.

Objective
To assess the silver ion release profile of a silver-containing hydrogel wound dressing over an 8-day period and thereby establish guidelines for its efficacious application.

Results Concentration of Ag+ Versus Time in Water

Concentration of Silver Ion (ppm)
120 100 80 60 40 30 20 0
18.8 8.21 11.9

Discussion
*Top liner detached on Day 5 **Top liner detached on Day 3

Introduction

Day 1 Day 9
90.2

102.0

71.7

Levels of silver cations (Ag+) retrieved were lower in NS than water at both Day 1 and Day 9. This finding was also described in another study using similar methodology.8 Although de-ionized water and NS are not true substitutes for wound fluid, they provide models of what might be expected in vivo.9 Silver ion release has been shown to be higher in models where albumin has 8,10 been added to water or saline as a better approximation of wound exudate; therefore, it may be anticipated that these levels are lower than what may be anticipated in vivo. Over time, the silver fibers throughout the dressing (rather than just superficial areas) may become more saturated, allowing for more silver cation release at the later time period tested (Day 9).8 Silver-release evaluations cannot be meaningfully compared across studies using different elution solutions, so direct comparisons with other studies are difficult to make.

Methods
The silver ion release profile was investigated in triplicate after a 24-hour incubation period (Day 1) and after eight 24-hour incubation periods (Day 9). Two studies were conducted, one using de-ionized water, and a verification study was conducted using 0.9% sodium chloride solution (normal saline [NS]) in place of water. Silver hydrogel samples (each about 4.84.9 g in de-ionized water or about 12.313.0 g in NS) were incubated in a water bath at 37C for 24 hours. The top liners were left in place. The bottom release layers were removed to simulate placement on a wound surface. Water volume was based on the hydrogel starting weight at a ratio of 1:100. NS volume was based on the hydrogel starting weight at a ratio of 1:6. Water or NS was replaced every 24 hours. The volume of each change was based on the hydrogel starting weight. The liquid removed after the initial 24-hour period and after the eighth 24 -hour period was retained. The silver ion concentration of the retained samples was measured by atomic absorption spectrometry (PerkinElmer, Waltham, MA). Silver Ion Hydrogel Dressing (12x magnification)

Methods

Sample 1*

Sample 2

Sample 3**

1:100 Silver/Hydrogel : Puried Water Bath

Concentration of Ag+ Versus Time in Normal Saline

Concentration of Silver Ion (ppm)
6 5 4 3 2 1 0 Sample 1 Sample 2 Sample 3
2.89

Day 1 Day 9

5.01

4.72 4.58 3.62 3.68

Conclusions
The silver fiber hydrogel wound dressing tested delivers a sufficient, sustained concentration of silver ion to provide antimicrobial activity for up to 8 days in both water and NS solution in vitro. Higher concentrations of silver ion were detected when dressings were incubated in de-ionized water compared to NS solution. Findings from both of these studies support a 7-day dressing change period.

Results and Conclusion

After 24 hours, the concentration of Ag+ was >8 to >18 ppm. After 8 days, the concentration of Ag+ was >71 to 102 ppm. The authors conclude that the silver fiber hydrogel wound dressing tested delivers a sufficient, sustained concentration of Ag+ to provide antimicrobial activity for up to 8 days. These findings support a 7-day dressing change period.
*SilverSeal Hydrogel Dressing (Alliqua Inc., New York, NY)

1:6 Silver/Hydrogel : Normal Saline Bath

References
AAnalyst 200
1. International consensus. Appropriate use of silver dressings in wounds. An expert working group consensus. London, England: Wounds International, 2012. Available at: www.woundsinternational.com. 2. Lindsay S. Silver White Paper. Everything you ever wanted to know about the use of silver in wound therapy. 2011 (Jan) Systagenix. 3. Winjhoven S, Peijnenburg WM, Herberts C, et al. Nanosilvera review of available data and knowledge gaps in human and environmental risk assessment. Nanotoxicology. 2009;3(2):109-138.

Introduction: SIlver Chemistry

Elemental silver is relatively unreactive; the antibacterial action of silver is dependent on the release of silver cations (Ag+) and is proportional to its concentration and availability to interact with bacterial and fungal cell membranes.1,3 Silver ions adhere to bacterial cell walls and plasma membranes, causing cell lysis and interfering with electron transport, and prevent DNA replication and 2,4 protein synthesis. Although studies have shown in vitro cytotoxic effects of silver ions on fibroblasts, the use of silver ion-containing dressings provide an environment that promotes more rapid healing.5-7

4. Chaloupka K, Malam Y, Seifalam AM. Nanosilver as a new generation of nanoproduct in biomedical applications. Trends Biotechnol. 2010;28(11):580-588. 5. Lo SF, Chang CJ, Hu WY, Hayter M, Chang YT. The effectiveness of silver-releasing dressings in the management of non-healing chronic wounds: a meta-analysis. J Clin Nurs. 2009;18(5):716-728. 6. Lara HH, Garza-Trevio EN, Ixtepan-Turrent L, Singh DK. Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds. J Nanobiotech. 2011;9:30. 7. Hiro ME, Pierpont YN, Ko F, et al. Comparative evaluation of silver-containing antimicrobial dressings on in vitro and in vivo processes of wound healing. ePlasty. 2012;12(e48):Epub 2012 Oct 11. 8. Lindsay S, DelBono M, Stevenson R, Stephens S, Cullen B. The silver release profile of antimicrobial wound dressings: standardizing in vitro evaluations. Presented at the 23rd Annual Symposium on Advanced Wound Care and Wound Healing Society (SAWC/WHS); Orlando, FL: April 17-20, 2010. 9. Lansdown AB. Silver in health care: antimicrobial effects and safety in use. Curr Probl Dermatol. 2006;33:17-34. 10. Landsdown AB. A pharmacological and toxicological profile of silver as an antimicrobial agent in medical devices. Adv Pharmacol Sci. 2010:910686.

The 2013 Spring Symposium on Advanced Wound Care (SAWC), May 15, 2013 Denver, Colorado