Targeted drug delivery

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Abstract
Cancer chemotherapy drugs are neither specific, i.e., they do not act exclusively on the metabolic pathways of cancer cells, nor are they targeted solely toward cancer cells. However, recent research has begun to address, in part, the latter issue. Improved delivery of chemotherapeutic agents to tumor tissue in man appears to be an achievable goal in the next decade. Improved drug delivery includes developing predictive models that allow for laboratory assessment of the best treatment for a patient's cancer without exposing the patient to an empirical trial or to the possible morbidity from exposure to a less useful drug, or to the loss of time in the fight against cancer because of ineffectual therapy. Monoclonal antibodies directed against tumor-associated antigens have the potential to achieve major advances in targeted drug delivery. Monoclonal antibodies may have direct antitumor effects, or they can be used as “homing devices” when attached to a payload and can guide diagnostic or therapeutic agents to the targeted tissues. Carrier systems of all types have become available; these include liposomes and polymeric compounds which can carry drugs, radionuclides, toxins, or other materials in a protected environment. These carriers can also be bound to monoclonal antibodies for possible targeted delivery. Pharmacological sanctuaries have been recognized as a problem in cancer treatment. The best known of these is the central nervous system (CNS). Techniques to temporarily disrupt the blood-brain barrier are now appearing. Mechanisms to administer therapy directly into the CNS are also being reassessed. Implantable pumps and reservoirs have been used to treat selected organs or for regional perfusions. Other treatments that are regional in scope include administration directly into a cavity or into a tumor. Computerized implantable devices should play a major role in cancer therapy in the future, in pain control as well as antibiotic and hormone administration. In recent years, mathematical models have been developed that can more accurately predict drug distribution and metabolism in various tissues of the body. Such models point the way to more logical designs of chemotherapeutic administration. The expanded use of autologous bone marrow transplantation, along with improving techniques of “purging” the marrow of tumor cells before reinfusion can be anticipated. Pro-drugs are substances that must be biotransformed in vivo to exert their pharmacologic effect. Certain pro-drugs that may be more effective or resistance-avoiding analogues of estab lished chemotherapeutic drugs are currently under development and offer considerable promise. A new era of improved drug delivery is achievable and can lead to greater efficacy of treatment regimens and a higher cure rate while at the same time reducing toxicity. This discussion deals primarily with the currently emerging therapies of monoclonal antibodies, liposomes and intra-arterial infusions. Cancer 58:573-583, 1986.