Abstract
We have obtained structure-activity relations for nanosphere drug delivery as a function of the chemical properties of a tunable family of self-assembling triblock copolymers. These block copolymers are synthesized with hydrophobic oligomers of a desaminotyrosyl tyrosine ester and diacid and hydrophilic poly(ethylene glycol). We have calculated the thermodynamic interaction parameters for the copolymers with anti-tumor drugs to provide an understanding of the drug binding by the nanospheres. We find that there is an optimum ester chain length, C8, for nanospheres in terms of their drug loading capacities. The nanospheres release the drugs under dialysis conditions, with release rates strongly influenced by solution pH. The nanospheres, which are themselves non-cytotoxic, deliver the hydrophobic drugs very effectively to tumor cells as measured by cell killing activity in vitro and thus offer the potential for effective parentarel in vivo delivery of many hydrophobic therapeutic agents.
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