RESUMO
Animal models are extensively used to evaluate the in vivo functionality of novel drug delivery systems (DDS). However, many variations likely exist in vivo between the animals and human physiological environment that significantly alter results obtained with animal models relative to human system. To date, it is not clear if the variation in hemorheology and hemodynamics between common animal and human models affect the functionality of DDS. This study investigates the role of hemorheology of humans and various animal models in dictating the binding efficiency of model vascular-targeted carriers (VTCs) to the wall in physiological blood flows. Specifically, the adhesion of sLe(A)-coated nano- and micro-spheres to inflamed endothelial cells monolayers were conducted via a parallel plate flow chamber assay with steady and disturbed red blood cells (RBCs)-in-buffer and whole blood flows of common animal models. Our results suggest that the ratio of carrier size to RBC size dictate particle binding in blood flow. Additionally, the presence of white blood cells affects the trend of particle adhesion depending on the animal species. Overall, this work sheds light on some deviation in VTC vascular wall interaction results obtained with in vivo animal experimentation from expected outcome and efficiency in vivo in human.
Assuntos
Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Eritrócitos/metabolismo , Hemodinâmica/fisiologia , Hemorreologia/fisiologia , Adulto , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Adesão Celular , Tamanho Celular , Células Cultivadas , Portadores de Fármacos/química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos , Microesferas , Método de Monte Carlo , Nanosferas/química , Tamanho da Partícula , Coelhos , Especificidade da Espécie , SuínosRESUMO
Continuous ambulatory peritoneal dialysis (CAPD) is utilized with increasing frequency for patients with end stage renal disease (ESRD). Several complications have been observed including catheter malfunction due to pericatheter leaks, abdominal wall and inguinal hernias and diaphragmatic leaks. Occasionally special diagnostic procedures are necessary to determine the nature of the abnormality and guide the surgical approach to correction. The four cases herein illustrate the usefulness of radionuclide imaging in diagnosing leakage of dialysate fluid in patients on CAPD.