Encapsulated Hemoglobin: Current Issues and Future Goals

Abstract

The promise of encapsulation systems for the sequestration of hemoglobin has been the long-held belief that encapsulation more closely mimics nature's strategy for circulating hemoglobin, and could alleviate hemoglobin based toxicities and increase circulation persistence. Various polymers have been proposed to deliver hemoglobin. One approach toward the encapsulation of hemoglobin has been to employ biodegradable, biocompatible vehicles such as phospholipid vesicles, or liposomes. The majority of encapsulation work with hemoglobin over recent years has focused on liposome encapsulated hemoglobin with demonstrations of efficacy and safety in total and partial isovolemic and hypovolemic exchange models, hemodynamics, circulation persistence and organ biodistribution, processing methods, long term storage through freeze-drying, and serum changes and histopathological consequences following administration in small animals. The data collected thus far indicate that encapsulation of hemoglobin does significantly alter many of the traditionally observed effects following the administration of cell free hemoglobin solutions. Liposome encapsulated hemoglobin circulates for 20–24 hours in small animals and principally distributes to the liver and spleen. The significant accumulation of liposome encapsulated hemoglobin in these organs poses new questions for short and long-term effects on the reticuloendothelial system and macrophage function which are currently being addressed. In addition, transient hemodynamic and serum changes have been observed following the administration of liposome encapsulated hemoglobin. Many of these are similar to the effects observed following administration of liposomes without intravesicular hemoglobin and are dictated by liposome parameters such as surface charge and character, size, and lipid composition. Finally, fundamental large scale production issues such as encapsulation efficiency and particle size distribution must be optimized to facilitate the commercial development of encapsulated hemoglobin. These issues are discussed in the historical context of encapsulated hemoglobin and basic liposome research, current research status, and future challenges for the development of encapsulated hemoglobin as an artificial oxygen carrying fluid.