Abstract

72Theoretically, a diseased body compartment can be treated by administration of relevant drug into that biological unit; however, use of any conventional route of drug administration, e.g., intravenous (i.v.), intra-arterial (i.a.), or oral, does not allow drug to be concentrated in the area of interest without its comparable distribution to remaining healthy compartments of the body. This in turn requires administration of large amounts of drug, most of which is metabolized by normal tissues. In situations in which drug with low therapeutic index is prescribed, the amounts required for building up the effective concentrations in the diseased area may be too toxic for the remaining healthy tissues in the body. This is particularly true with all chemotherapeutic agents, which are an essential part of most cancer treatment schedules. 1 , 2 Hence, increased efforts have been made to confer regional or targeted drug delivery to diseased tissue or cells with reduced drug exposure to the normal cells. 2 , 3 It has been suggested that the therapeutic and toxic effects with cytotoxic agents are so closely balanced that even a slight change in drug distribution in favor of target tissue may be beneficial. 1 Hence, any approach that can improve tumor versus nontumor distribution of these agents is expected to increase their therapeutic efficacy. Attempts to improve therapeutic efficacy in cancer chemotherapy using modified dosage regimens, such as long-term low-dose infusion or short-term high-dose infusion of cytotoxic agents, have generally demonstrated limited benefit. 4–8 Hence, over the last two decades, several alternative drug delivery methods have been investigated for controlling the in vivo distribution of chemotherapeutic agents, including macromolecular drug conjugates 9 and a variety of particulate microcarrier systems with built-in specific characteristics, such as predetermined size, prolonged blood circulation time, responsiveness toward pH, temperature and magnetic field, reaction with target cell-specific epitopes, and controlled release of drug in situ. 10–14 Pharmacokinetic rationales of regional drug delivery have suggested the possibility of further improvement in chemotherapy following i.a. administration. 4 , 15 Among various regional drug delivery approaches, magnetically responsive systems have received considerable attention for targeted delivery of chemotherapeutic agents. 16 , 17 This chapter reviews the current status of this drug delivery method with particular emphasis on its application in the treatment 73of localized tumors. Following a brief discussion on the fundamentals and classification of drug targeting, the experiments conducted so far toward the development and evaluation of biodegradable and nonbiodegradable magnetically targeted drug delivery systems are summarized. Because magnetic albumin microspheres represent one of the most thoroughly investigated drug carriers for targeted chemotherapy, 16 , 17 detailed information on their methods of preparation, in vitro characterization, and efficacy in chemotherapeutic treatments is presented. Finally, the chapter outlines the future prospects and general limitations of magnetically controlled delivery systems in cancer chemotherapy.

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