Use of polymeric drug delivery systems is rapidly becoming an established approach for improvement of
cancer chemotherapy.
Zoladex, a
poly lactide-co-glycolide subcutaneous implant that delivers a
luteinizing hormone releasing hormone analog over 28 days, is now the treatment of choice for
prostate cancer, and a polyanhydride matrix containing
BCNU is currently in phase III evaluation for treatment of
glioma multiforme. Soluble
polymers were first proposed as targetable
drug carriers in the mid-1970s, and although the first conjugates are still at an early stage of development some, e.g.
SMANCS (
styrene maleic acid-
neocarzinostatin) and monomethoxypolyethyleneglycolasparaginase, are now undergoing clinical evaluation and show considerable promise. Polymeric drug delivery systems are usually designed to produce an improved pharmacokinetic profile of an
antitumor agent (controlled release) and in addition soluble carriers can achieve either first-order (organ specific) or second-order (
tumor specific) drug targeting by virtue of the fact that they are usually administered intravenously and should theoretically access primary and secondary disease. Soluble polymeric carriers have the potential to improve the activity of conventional
antitumor agents,
peptide and
protein drugs, and have recently been used in constructs for delivery of
oligonucleotides. With increased awareness that the successful design of a polymeric drug delivery systems can only be achieved with prior consideration of the pathology and stage of the disease,
tumor accessibility, biochemistry and cell biology of the target site, choice of appropriate therapeutic agent(s) and understanding of their fundamental mode of action, we have seen the emergence of a number of exciting and potentially more selective antitumor
therapies based on
polymer technologies. Here, the basic principles for design of soluble polymeric drug delivery systems are explained and illustrated using examples drawn from our studies on the development of
N-(2-hydroxypropyl)methacrylamide copolymer conjugates for use in
cancer chemotherapy. Those soluble polymeric carriers that are undergoing clinical evaluation are briefly reviewed.