In the field of resorbable devices, drug eluting sutures represent an applied research field on which the reliability of both production processes and mathematical prediction modeling were tested. Indeed, poly-e-caprolactone pellets were compounded with lidocaine and then extruded to obtain highly loaded threads. The complete and rapid release demonstrated that the extrusion process does not alter the drug, which is confirmed to be embedded in an open porous matrix, being free to be solvated by uptaken water and to diffuse. Release profile and polymer degradation were simulated through a mathematical model based on conservation laws that allowed to assess release kinetic and to confirm the understanding of involved phenomena, as it fit experimental data. Reliability and robustness of chosen model allow to monitor the overall quality of manufacturing because any discrepancy between experimental and simulated data can be adopted to assess drug distribution uniformity within the device.
SummaryHuman umbilical vein endothelial cells (HUVEC) were cultivated on globular microcarriers in order to improve the endothelial cell surface to blood-volume ratio over the conventional flat bed cultures. HUVEC-beads were tested for their modulation of blood coagulation using a combination of two steps: HUVEC-beads were added into the syringe used for the venipuncture, in order to achieve immediate contact between cells and blood, and no anticoagulant was used during the incubation time of HUVEC-beads with whole blood. The coagulation initiation produced by venipuncture was almost completely suppressed as judged by thrombin measurements over a period of 60 min. The activated partial thromboplastin time showed a prolongation by a factor >3. Direct measurements of activated protein C (APC) were negative. Moreover, inhibition of APC-generation with a monoclonal anti-human protein C antibody did not affect the anticoagulant properties of endothelial cells. Therefore the anticoagulant properties exerted by HUVEC-beads are not dependent on APC.
In an attempt to create the possibility of stable, long acting, intravascular anticoagulation, low molecular weight heparin was modified by introducing a sulfhydryl group into the molecule (LMWH-SH). Human erythrocytes were covalently grafted with LMWH-SH by the use of a heterobifunctional coupling reagent which reacts with the SH group of LMWH-SH and surface exposed amino groups of erythrocytes now called`heparinocytes' (HC). HC were morphologically indistinguishable from untreated erythrocytes and displayed identical osmotic resistance. The functionality of HC was analyzed by classical coagulation tests in which they dose dependently inhibited clot formation. HC were also functional in recalcified whole blood inhibiting thrombin formation as assessed by the cleavage of the chromogenic substrate S-2238. The system appears applicable as a potential autologous, long-term anticoagulant treatment or prophylaxis.z 2000 Federation of European Biochemical Societies.
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