title: Sustained release carrier for adenosine triphosphate as signaling molecule.
abstract: Adenosine triphosphate (ATP) is a molecule with a fascinating variety of intracellular and extracellular biological functions that go far beyond energy metabolism. Due to its limited passive diffusion through biological membranes, controlled release systems may allow to interact with ATP-mediated extracellular processes. In this study, two release systems were explored to evaluate the capacity for either long-term or short-term release: (i) Poly[(rac-lactide)-co-glycolide] (PLGA) implant rods were capable of ATP release over days to weeks, depending on the PLGA molecular weight and end-group capping, but were also associated with partial hydrolytic degradation of ATP to ADP and AMP, but not adenosine. (ii) Thermosensitive methylcellulose hydrogels with a gelation occurring at body temperature allowed combining adjustable loading levels and the capacity for injection, with injection forces less than 50N even for small 27G needles. Finally, a first in vitro study illustrated purinergic-triggered response of primary murine microglia to ATP released from hydrogels, demonstrating the potential relevance for biomedical applications.
authors.affiliation: Institute of Biomaterial Science, Helmholtz-Zentrum Geesthacht, Kantstr. 55, Teltow, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Kantstr. 55, Teltow, Germany. Electronic address: christian.wischke@hzg.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Wischke
authors.affiliation: Institute of Biomaterial Science, Helmholtz-Zentrum Geesthacht, Kantstr. 55, Teltow, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Kantstr. 55, Teltow, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Weigel
authors.affiliation: Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, Berlin, Germany.
authors.forename: Larisa
authors.initials: L
authors.lastname: Bulavina
authors.affiliation: Institute of Biomaterial Science, Helmholtz-Zentrum Geesthacht, Kantstr. 55, Teltow, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Kantstr. 55, Teltow, Germany. Electronic address: andreas.lendlein@hzg.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lendlein
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001831:Body Temperature; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry; D008747:Methylcellulose / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D017628:Microglia / Q000378:metabolism; D011098:Polyglactin 910 / Q000008:administration & dosage / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D011098:Polyglactin 910; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D008747:Methylcellulose
keywords: Adenosine triphosphate; Controlled release carrier; Methyl cellulose hydrogel; Microglia cells; PLGA implant rods