Immuno‐isolation protects islet tissue from rejection by enclosing it within semi‐permeable membranes. Four major techniques have been developed to achieve this goal: (1) Extravascular diffusion chambers. These can be implanted in many locations but are limited by host fibroblastic responses which further reduce diffusion capability. (2) Intravascular diffusion chambers. These have improved diffusion characteristics dependent on design but have serious vascular access problems. (3) Intravascular ultrafiltration chambers. These have a more rapid response since they do not rely on diffusion but have an additional problem of protein deposition on their membranes. (4) Microencapsulation. This technique incorporates the islet tissue inside a biochemical membrane making it more efficient. Yet the technique is limited by membrane instability. Immuno‐isolation offers an alternative to immunosuppression, but the biotechnology must be improved to develop suitable materials for effective clinical trials.
Collagenase covalently attached to cellulose acetate membranes, following periodate activation of the membrane, maintained its enzymatic activity and permanence of attachment for more than 6 weeks. The length of spacer between the enzyme and the membrane was studied with enzymes attached directly, through ethylenediamine and through ethylenediamine plus succinnic anhydride. Enzyme activity was measured by determining the degradation rate of a pigskin gelatin solution, and stability of the bond was measured by observing continued degradation after the enzyme-membrane was removed from the solution. The longest spacer resulted in the highest enzyme activity. I nterest is growing rapidly in supplying blood glucose control in diabetics through the use of chambers in which Islets of Langerhans are interfaced with the blood supply through a permeable membrane. The object is to provide adequate insulin release in response to blood glucose, while isolating the cells from immune response. Consideration is being given to both intravascular and extravascular islet-transplantation chambers. A problem that arises in the consideration of an extravascular device is that synthetic materials placed in the body tissues rapidly become covered with cells (polymorphonuclear leukocytes and macrophages) and surrounded with relatively impervious fibrous tissue. This could decrease the diffusion rates of glucose and insulin, eventually rendering a chamber useless. One possible solution to this problem is the attachment of proteolytic enzymes to the surface of the chamber to prevent formation and attachment of fibrous tissue at the interface. It was reported by Jolley (1 ) that a cellulosic chamber (Millipore Corporation) coated with covalently bound collagenase and implanted in the rat
Schistosomiasis is among the top five diseases in the world in terms of morbidity, affecting perhaps 200 million people in tropical and subtropical countries. Antischistosomal drugs are toxic and rapidly metabolized. Hence, they must be given in a number of spaced doses. In spite of this there are severe side effects leading to poor patient compliance. This is an ideal situation for the application of sustained drug release to avoid the toxic peak concentration of drug. This study was carried out using Astiban acid, an antimonial drug that is effective against S. mansoni. Unfortunately, the drug is sufficiently soluble that 50 mg will dissolve in 100 mL water in less than a minute. To permit sustained release of intramuscularly injected drug, microcapsules of astiban acid in poly(d,l-lactic acid) were formed by coacervation. Release studies show that an appreciable fraction of the drug is available at the surface for rapid solution. After this surface drug dissolves, the remaining drug is released slowly with half-times of many hours. After the initial burst, the release of drug follows Higuchi's equation up to approximately 80% release, with exponentially decreasing release rates thereafter.
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