Drug-loaded erythrocytes: on the road toward marketing approval.

Erythrocyte drug encapsulation is one of the most promising therapeutic alternative approaches for the administration of toxic or rapidly cleared drugs. Drug-loaded erythrocytes can operate through one of the three main mechanisms of action: extension of circulation half-life (bioreactor), slow drug release, or specific organ targeting. Although the clinical development of erythrocyte carriers is confronted with regulatory and development process challenges, industrial development is expanding. The manufacture of this type of product can be either centralized or bedside based, and different procedures are employed for the encapsulation of therapeutic agents. The major challenges for successful industrialization include production scalability, process validation, and quality control of the released therapeutic agents. Advantages and drawbacks of the different manufacturing processes as well as success key points of clinical development are discussed. Several entrapment technologies based on osmotic methods have been industrialized. Companies have already achieved many of the critical clinical stages, thus providing the opportunity in the future to cover a wide range of diseases for which effective therapies are not currently available

Tennis play intensity distribution and relation with aerobic fitness in competitive players

15 p.Los objetivos de este estudio fueron (1) describir la intensidad relativa del juego de tenis simulado en función del tiempo acumulado en tres zonas de intensidad metabólica y (2) determinar las relaciones entre esta distribución de intensidad de juego y la aptitud aeróbica de un grupo de jugadores competitivos. 20 jugadores masculinos de nivel avanzado a élite (ITN) realizaron una prueba de tenis de resistencia específica en el campo incremental hasta el agotamiento para determinar el consumo máximo de oxígeno (VO2max) y los umbrales de ventilación primero y segundo (VT1, VT2). Los parámetros de ventilación y de intercambio de gases se monitorizaron utilizando un analizador de gas portátil telemétrico (K4 b2, Cosmed, Roma, Italia). Dos semanas después, los participantes jugaron un juego de tenis simulado contra un oponente de nivel similar. Las zonas de intensidad (1: baja, 2: moderada y 3: alta) fueron delimitadas por los valores individuales de VO2 correspondientes a VT1 y VT2, y se expresaron como porcentaje del VO2 máximo y la frecuencia cardíaca. Cuando se expresó en relación con el VO 2 máx. El porcentaje de tiempo de juego en la zona 1 (77 ± 25%) fue significativamente mayor (p <0,001) que en la zona 2 (20 ± 21%) y la zona 3 (3 ± 5%). Se encontraron correlaciones positivas de moderadas a altas entre VT1, VT2 y VO2max, y el porcentaje del tiempo de juego transcurrido en la zona 1 (r = 0,68-0,75), así como las correlaciones inversas de bajas a altas entre las variables metabólicas y el porcentaje de tiempo empleado en las zonas 2 y 3 (r = -0.49–0.75). Los jugadores con mejor aptitud aeróbica juegan a intensidades relativamente más bajas. Concluimos que los jugadores pasaron más del 75% del tiempo en su zona de baja intensidad, con menos del 25% del tiempo dedicado a intensidades moderadas a altas. La aptitud aeróbica parece determinar la intensidad metabólica que los jugadores pueden mantener durante todo el juegoS

Pacing and Decision Making in Sport and Exercise: The Roles of Perception and Action in the Regulation of Exercise Intensity

In pursuit of optimal performance, athletes and physical exercisers alike have to make decisions about how and when to invest their energy. The process of pacing has been associated with the goal-directed regulation of exercise intensity across an exercise bout. The current review explores divergent views on understanding underlying mechanisms of decision making in pacing. Current pacing literature provides a wide range of aspects that might be involved in the determination of an athlete's pacing strategy, but lacks in explaining how perception and action are coupled in establishing behaviour. In contrast, decision-making literature rooted in the understanding that perception and action are coupled provides refreshing perspectives on explaining the mechanisms that underlie natural interactive behaviour. Contrary to the assumption of behaviour that is managed by a higher-order governor that passively constructs internal representations of the world, an ecological approach is considered. According to this approach, knowledge is rooted in the direct experience of meaningful environmental objects and events in individual environmental processes. To assist a neuropsychological explanation of decision making in exercise regulation, the relevance of the affordance competition hypothesis is explored. By considering pacing as a behavioural expression of continuous decision making, new insights on underlying mechanisms in pacing and optimal performance can be developed. © 2014 Springer International Publishing Switzerland

In vitro studies of amikacin-loaded human carrier erythrocytes

Erythrocyte-encapsulated antibiotics have the potential to provide an effective therapy against intracellular pathogens. The advantages over the administration of free antibiotics include a lower systemic dose, decreased toxicity, a sustained delivery of the antibiotic at higher concentrations to the intracellular site of pathogen replication, and increased efficacy. In this study, the encapsulation of amikacin by human carrier erythrocytes prepared using a hypo-osmotic dialysis was investigated. The effects of the initial amikacin dialysis concentration and hypo-osmotic dialysis time on the encapsulation efficiency of amikacin were determined, and the osmotic fragility and hematologic parameters of amikacin-loaded carrier erythrocytes were measured. The efficiency of amikacin entrapment by carrier erythrocytes was dependent on the initial dialysis concentration of the drug. Statistically significant differences in the osmotic fragility profiles between control and carrier erythrocytes were observed, which were dependent on the hypo-osmotic dialysis time and on the dialysis concentration of amikacin. Mean hematologic parameters were evaluated and compared with unloaded, native erythrocytes; the mean corpuscular volume (MCV) of amikacin-loaded carrier erythrocytes was statistically significant smaller. Amikacin demonstrated a sustained release from loaded erythrocytes over a 48-h period, which suggests a potential use of the erythrocyte as a slow systemic-release system for antibiotics