ABSTRACT
Artificial cells containing concentrated hemoglobin (Hb) solution were prepared by interfacial polymerization of Hb with glutaraldehyde (GA) in liquid membrane capsules (LMC). A solution containing 30% of Hb was emulsified in mineral oil as red cell-size microdroplets, and this emulsion was dispersed in an aqueous phase containing glutaraldehyde to form LMC. The LMC were semipermeable templates that held the microdroplets of Hb in suspension while GA diffused through the oil to the microdroplet surfaces. The GA crosslinked Hb at the surface of each microdroplet to form an artificial red-cell membrane encapsulating Hb solution. A water-soluble surfactant was used to eject the cells from the LMC and suspend them in saline. Several surfactants were evaluated. Cell size was controlled by agitation speed during preparation of the original emulsion. Cells of 2.52 = +/- 1.69 micron were prepared. The encapsulated Hb retained capacity to bind and release O2. The cells had a P50 of 8.9 torr (1200 Pa) and a capacity of 0.55 cc O2/g of total Hb, indicating that the crosslinked portion of the Hb did not contribute to O2 transport.
Subject(s)
Blood Substitutes , Capsules , Cross-Linking Reagents , Glutaral , Hemoglobins , Humans , Membranes, Artificial , OxygenSubject(s)
Blood Substitutes , Hemoglobins , Animals , Biodegradation, Environmental , Cross-Linking Reagents , Glutaral/pharmacology , RatsSubject(s)
Urease/administration & dosage , Uremia/therapy , Administration, Oral , Animals , Blood Urea Nitrogen , Capsules , Dogs , Uremia/bloodABSTRACT
The objective of the program is to use ingested liquid membrane capsules (LMC) as gastrointestinal toxin traps as an adjunct to dialysis. Urea has been selected as the model toxic component to study before expanding the technology to other toxins. Transport across the small intestinal mucosa has been indicated to be adequate. There is no indication of reduction of mucosal transport or damage to the intestinal mucosa over short term but repetitive LMC perfusions. Performance of LMC perfused through Thiry Vella small intestinal loops is as good as in vitro performance and can be predicted. Substantial progress has been made toward developing LMC to perform in the more complex environment of the intact gastrointestinal tract. The demonstration of LMC performance in vivo with intact gastrointestinal tracts, and perhaps some increase in rate of toxin removal, will be required before LMC can be considered practical candidates for clinical use.
Subject(s)
Antitoxins/administration & dosage , Uremia/therapy , Administration, Oral , Capsules , Humans , Membranes , Methods , Renal DialysisSubject(s)
Emulsions , Uremia/therapy , Absorption , Ammonia/analysis , Animals , Blood Urea Nitrogen , Chronic Disease , Dogs , Intestine, Small/analysis , Methylguanidine , Urea/analysis , Urease/pharmacology , Uremia/bloodABSTRACT
An attempt is being made to develop an oxygenator utilizing gaseous oxygen bubbles completely encapsulated with fluorochemical, thereby avoiding the detrimental changes induced by a blood-gas interface. After the feasibility of this method of oxygenation had been proved, the biocompatibility of the fluorochemicals was investigated. No significant changes in human red blood cells, fibrinogen, or platelets were induced by chronic in vitro contact with fluorochemical over a 24-hour peroid. There is no evidence that the fluorochemicals tested extract lipids from plasma. A device which allowed continuous formation of a blood-fluorochemical interface was utilized in vitro with human blood and in vivo with dogs. No significant alterations were induced by fluorochemicals in the human or animal blood or in the canine organs at autopsy. A prototype oxygenator is now undergoing evaluation. A method of analyzing for fluorochemical in blood and other protein solutions is presented.