Enzyme-protein conjugates: new possibilities for enzyme therapy

It has become apparent in the past few years that a variety of approaches to treating enzyme deficiency diseases and specifically for the delivery of drugs/enzymes to specific sites will be required to overcome the various limitations to simple drug or enzyme administration. It is now evident that no one carrier system will prove a panacea to tackle all of the situations where carrier systems may be required (Gregoriadis, 1976). In one case we may require that an enzyme remain for a prolonged period within the circulation, in another delivery of enzyme to phagocytic tissue may be required whereas in a third case it may be essential that the reticuloendothelial system be avoided in order that delivery to specific tissues be achieved. Under certain circumstances where enzymes may have to move from the plasma past endothelial barriers to tissue such as muscle, it may be important to retain the enzyme within the circulation in order to allow a maximum amount of the enzyme or enzyme-carrier complex to permeate the endothelial barrier. Consideration must also be given to the effects of the enzyme/drug on nontarget tissue. In the case of antitumor agents and perhaps even toxins such as ricin toxin or diphtheria toxin a high efficiency targeting to tumor tissue may be required because of the high toxicity and adverse effects of the product on normal tissue. In other cases the deposition of enzymes or drugs in nontarget tissue will have little adverse effects. In addition to questions of drug/enzyme delivery, consideration must be given to the rates of biodegradation of enzyme and/or drug following repeated intravenous administrations as well as the immunological complications that may ensue from the administration of foreign proteins or drugs attached to carrier molecules which may now assume the immunological properties of haptens. We now have a sufficient number of different carrier systems with varying properties that we can consider tailoring the carrier system to the specific requirements of the disease condition under consideration be it specific targeting, avoiding biodegradation or immunological attack, alterations in pH characteristics of the carried agent or increasing the circulation half-life of the therapeutic agent. We now have the opportunity to tailor a carriage system to the requirements of a specific disease rather than search for a disease to suit the characteristics of a specific carrier system.