Poly( n -butylcyanoacrylate) Nanoparticles as Carriers for Adenosine triphosphate
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Poly(n-butylcyanoacrylate) Nanoparticles as Carriers for Adenosine triphosphate Christian Wischke, Judith Weigel and Andreas Lendlein Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Kantstr. 55, 14513 Teltow, Germany ABSTRACT Adenosine triphosphate (ATP) has numerous biological functions both intra- and extracellularly, including effects on the directed migration of cells with a regenerative potential in brain tissue. Therefore, carrier systems would be of interest that would be capable to be loaded with ATP and release it in a controlled manner. In the present study, poly(n-butylcyanoacrylate) (PBCA) nanoparticles as a potential carrier system were prepared by anionic polymerization using different polymerization media, which resulted in different zeta potential values and in some cases aggregation of nanoparticles. By decorating the particle surface with positively charged diethylaminoethyl dextran, multivalent ionic interaction allowed to load ATP to the nanoparticles by adsorption. In release experiments, an ATP release over 6 hours was observed. ATP-loaded nanoparticles may thus be suitable to explore biological effects of short-term ATP delivery for biomedical applications. INTRODUCTION Substances with a chemotactic biological effect are often relatively large molecules and possibly sensitive to a loss of functionality by structural alterations in an artificial environment. However, there are also other types of substances reported that induce cellular chemotaxis according to a concentration gradient and thus may be useful to guide cells, e.g. to lesion sites in regenerative medicine. One of such substances with low molecular weight is adenosine triphosphate (ATP), a molecule well known for its role in energy metabolism. Beyond that, ATP can be assigned to various intra- and extracellular processes including, e.g., its capacity to act on microglia cells, which are immune cells of the central nervous system. As a substrate of ectonucleotidases expressed by microglia at their cell surface, extracellular ATP can eventually affect the cell’s activation status and induce cell migration [1]. Carrier systems that deliver ATP to a cellular environment may be useful to study and possibly facilitate ATP release for therapeutic purposes. However, so far only few carrier systems were reported for the controlled delivery of ATP. These include poly[(rac-lactide)-coglycolide] implant rods and hydrogels [2], chitosan nanoparticles [3], or mesoporous silica nanoparticles [3]. Some of these systems did not show degradability and injectability through small needles as would be desired for medical applications. Based on the chemical structure of ATP with three anionic moieties, it was hypothesized that multivalent ionic interactions may be capable to load ATP on a carrier system such as nanoparticles, which have a high surface to volume ratio. Considering that poly(nbutylcyanoacrylate) [PBCA] nanoparticles have been reported before as injectable carriers for drug delivery to the brain [4
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