V: Blood Purification
Advances in Nanostructured Carbons for Biomedical Applications
Susan Sandeman, Yishan Zheng, Ganesh Ingavle, Tochukwu Ozulumba, Carol Howell, and Sergey Mikhalovsky
School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, UK
Carbon adsorbents have a long history of use in medical devices for the removal of biotoxins known to exacerbate inflammation and infection. The traditional Western medical application for activated carbons has been limited predominantly to cases of poisoning and some wound dressings. However, technological advances in the synthesis of next generation, nanostructured carbon adsorbents in a range of forms combined with currently escalating challenges in the treatment of life-threatening infection and non-communicable disease have directed opportunities to repurpose and extend the
Carbon Nanomaterials in Biomedicine and the Environment
Edited by Zulkhair A. Mansurov
Copyright © 2020 Jenny Stanford Publishing Pte. Ltd.
ISBN 978-981-4800-27-3 (Hardcover), 978-0-429-42864-7 (eBook) www.jennystanford.com biomedical applications of these versatile materials. Research has begun to highlight aspects of biointerfacial phenomena which uniquely impact the adsorptive capacity of nanostructured carbons in biomedical applications. Additionally, carbon adsorbents with tailored, consistent and well defined nanoporosity allow removal of a wider size range of key biotoxins associated with disease progression allowing advances in the efficacy of oral enterosorbent, blood perfusion and wound dressing devices.
Carbon products are well known for their superior adsorptive properties and inert nature allowing their use medicinally for thousands of years . More recently the advent of synthetically sourced precursors and the development of highly controlled production routes have enabled the synthesis of a consistent activated carbon structure with highly developed and tuneable internal porosity . This in turn has presented a range of biomedical applications in which nanoporous activated carbons in addition to other 2 dimensional carbon allotropes can be used as highly efficient biotoxin adsorbers, targeting inflammatory mediators and toxic metabolites which promote systemic toxicity and bacterial products which promote systemic and life threatening infection [3-7]. Such materials may be used to improve the current adsorptive profile of devices already in use or by addition to multicomponent systems where variable patient susceptibility to systemic inflammatory stimulus exists. In addition, the rise in antimicrobial resistance and narrowing feasibility of effective antibiotic use presents an opportunity to develop carbon adsorbents with broadly developed affinity for bacterial products and capacity to suppress inflammatory stimulus.
Adsorbent technologies not involving carbon generally have defined and selective adsorptive targets. The benefit of carbon technology is that it is biocompatible, broadly acting, has a superior adsorptive surface area, can be tailored to extend adsorbate size range and is relatively cost effective. This gives an advantage for use in conditions where alternative augmentation strategies to treat biotoxin overload may remain cost prohibitive. As with the development of other biomedical products the progression of such adsorbent carbons to market depends on an interdisciplinary approach combining the expertise of carbon chemists, biotechnologists, clinicians and industrial partnerships to allow translational pathway focus. Activated carbon preparations must fit within a complex regulatory environment and categorisation as a medical device depends on a range of features including primary purpose. The medical device market has anticipated growth rates exceeding those of pharmaceuticals with predictions that nanomaterials will play a significant part in this growth. The cost, scale and length of testing under a pharmaceutics translational pathway are prohibitive for activated carbon where the mode of action is primarily physical.
The umbrella title of nanostructured carbons incorporates nanoporous activated carbons and can extend to 2-dimensional adsorbent graphene derivatives which have demonstrated a capacity for adsorption of inflammatory molecules . The nanoscale dimensions of graphenes bring additional biocompatibility issues when applying these materials to bioadsorption including concerns over inadvertent, damaging interactions with cellular processes, bioaccumulation within body organs and environmental accumulation of nanoparticles. For bead and nanoparticles a coating or composite formulation may address safety requirements assuming that issues of available surface area for adsorption are resolved. For perfusion devices, the synthesis of monolithic adsorbents limits systemic fine particle release, pressure drop across the system and reduces haemocompatibility issues.
Ultimately the biocompatibility and efficacy of any biomaterial depends on optimisation of the biointerface; the point at which the surface of the biomaterial meets the biological environment . In the case of activated carbon adsorption capabilities depend on the source material and activation conditions. These create an accessible internal surface area with pore dimensions that can control the size of molecules adsorbed. Physical adsorption occurs via weak van der Waals forces and depends on a number of influencing factors including diffusional rate, accessible surface area and solvent type. Adsorption is primarily of non-polar organic molecules with poor water solubility and is enhanced by the presence of an aromatic molecular structure. Use of synthetic resin precursors creates a consistent structure and nanoporous dimensions not seen in microporous carbons introducing a capacity for adsorption of high molecular weight biotoxins including inflammatory cytokines, bacterial lipopolysaccharides and exotoxins (Fig. 9.1). Such advances open up new possibilities for the re-introduction of nano-dimensional carbon products for medical device applications. This chapter will consider some recent developments in nanostructured carbons using a range of forms, allowing adaptation to clinical and environmental requirements. Primarily these applications are currently within organ replacement perfusion devices for detoxification, oral preparations for enterosorption and wound dressings.
Figure 9.1 The internal nanoporosity of activated carbon beads influences the size ofbiotoxins that can be removed by adsorption.