Got the bug?: Preventing microbial infections in medical plastics
Lawrence Acquarulo, Foster Corporation, looks in detail at antimicrobial masterbatches for medical plastics.
Hospital Infections
According to a survey by the Center for Disease Control (CDC), 4% of inpatients in US acute care hospitals contract at least one healthcare associated infection. Device associated infections accounted for one in every four. In-dwelling devices, such as central venous (CV) catheters, are particularly susceptible to bacteria colonization which can enter the blood stream. Increasingly, medical device companies are evaluating antimicrobial additives for plastics used for susceptible devices. The resulting compounds are designed to kill harmful bacteria on the surface of device components.
Antimicrobial metals
Silver and copper have been used for thousands of years to prevent microbial infections. Yet the mechanism of action was not fully understood until recently. This began in the 19th century, when scientists discovered bacterial microorganisms caused infections. In recent years, scientists have discovered how certain metals destroy harmful microorganisms, including methicillin-resistant staphylococcus aureus (MRSA) and carbapenem-resistant enterobacteriaceae (CRE).
Metallic silver (Ag) is inert, insoluble in water, and unable to kill bacteria. However, when combined with certain elements (eg, chlorine) silver atoms lose an electron and become ionic (Ag+). This form of silver is colorless, water soluble, and highly reactive with other elements. Ionic silver attacks bacterial cell membranes making them more permeable. It also interferes with cell metabolism resulting in overproduction of reactive oxygen compounds that are toxic to the cells.
Copper is an important nutrient for cells, including bacteria. However, in high doses it is known to efficiently kill bacterial cells. Research into copper’s precise antimicrobial mechanism of action is ongoing and inconclusive. Yet a number of studies indicate that copper effects the integrity of the bacterial cell wall and inappropriately binds to proteins within the cell causing loss of function.
When used for infection control applications, these metals are often bound to inert carriers that impart chemical stability and extend the duration of antimicrobial action. Common organic carriers include zeolites, phosphates, titanium dioxide, montmorillonite and mesoporous silica.
Zeolites are particularly effective carriers for melt blending with medical plastics. These crystalline aluminosilicates are compositions of aluminum, silicon and oxygen, with uniform cavities and pores. This geometric construction controls release of the antimicrobial metals. Importantly, zeolites can withstand the high melt processing temperatures of thermoplastics.
Sciessent, a leading manufacturer of antimicrobial additives, has developed technology that incorporates both ionic silver and copper in a zeolite carrier. Marketed under the brand name Agion, this technology is designed to exchange silver ions with positive ions from moisture in the environment. The exchange releases antimicrobial elements only when conditions are ideal for bacterial growth.
The company reports Agion antimicrobial technology fights bacterial growth in three ways: it prevents respiration by inhibiting transport functions in the cell wall; it inhibits cell division and therefore limits the reproduction necessary for bacteria to colonize; and, disrupts cell metabolism.
Masterbatches for medical polymers
Foster Corporation has developed high concentration masterbatch formulations using Sciessent Agion technology in a universal polymer matrix. These were developed to be dry blended with unmodified polymers at letdown percentages from 2-10%, depending on the polymer and application. Dry blending with masterbatches allows engineers to cost effectively evaluate different antimicrobial loading levels in medical components.
Foster’s Combat AD masterbatch was developed using Agion AD85H-M (AD) antimicrobial additive; a fine particle zeolite (< 4 µm) and high proportioned ionic silver (20-24%). The masterbatch consists of 40% Agion AD and 60% ethylene vinyl acetate (EVA) -based universal polymer alloy carrier. Combat AD is designed to be used in TPU’s and silicones for indwelling devices such as CV catheters.
Combat AK master batch was developed using Agion LGK-10 (AK) antimicrobial additive; a large particle zeolite (> 6 µm) and a low proportioned ionic silver (4-6%). The masterbatch consists of 40% Agion AK and 60% EVA-based universal polymer alloy carrier. Combat AK is designed for ABS and PC polymers used for high-touch surface components and devices. These include bedrails, diagnostic equipment housings and instrument handles.
Foster and Sciessent recently completed a joint study to determine the efficacy of these masterbatches. A total of six formulations consisting of different Agion additive loadings in three polymers. The percentage of Agion antimicrobial additive indicated below represents the total amount in the final blend.
- TPU + Combat AD4 master batch (4% Agion AD)
- TPU + Combat AD8 master batch (8% Agion AD)
- ABS + Combat AK1 master batch (1% Agion AK)
- ABS + Combat AK3 master batch (3% Agion AK)
- PC + Combat AK1 master batch (1% Agion AK)
- PC + Combat AK3 master batch (3% Agion AK)
Antimicrobial properties of the TPU samples were tested according to ASTM E2149. Properties of the ABS and PC samples were tested according to ASTM E2180. These tests determine the kill rates of MRSA and CRE. For all six samples there was a 99.9999% microbial reduction, with log reductions between 6.4 and 6.8.
New options for medical products
Certain metals, such as silver and copper, have a long history of reducing infections. Plastic components made from formulations that incorporate these antimicrobial metals can reduce hospital infections related to medical devices. Traditionally, material suppliers melt blended these antimicrobial additives into plastics prior to processing. However, engineers evaluating multiple additive loading levels had to invest in several compounds for molding or extrusion trials.
An alternative approach uses master batches with high concentrations of metallic-based antimicrobial additives for dry blending with polymers immediately prior to molding or extrusion. This approach allows engineers to economically evaluate various antimicrobial loadings in the finished part using a single master batch. Recent tests confirmed effective microbial reduction using different master batch loadings in several common medical device polymers.