| 摘要 |
Microfabricated, asymmetrical, reservoir-containing particles for use in the intravenous delivery of cytotoxic agents such as melittin to tumors is disclosed. The particles have a selected shape and uniform dimensions preferably in the 1 mum to 10 mum range. The reservoirs open to the face of the particle and are filled with a solution or suspension of the therapeutic agent and selected excipients. The drug/excipient solution may be dried by standard techniques. The excipients are selected to delay the dissolution/release of the agent from the particle reservoirs for 1-48 hours after the particle suspension is rehydrated and injected. Alternatively, the pore is plugged with an erodable material or covered with a semipermeable membrane. The face of the particle is grafted with a layer of specific ligands designed to quickly bind the particle to the surface of either tumor cells or the vascular endothelial cells, which form tumor capillaries. The cytolytic agent, which is released from the reservoirs after binding, is presented directly to the surface membranes of target cells. The locally high concentration of cytolytic agent achieved in the circumscribed volume between the face of the particle and the juxtaposed cell provides for efficient entry of the cytolytic agent directly into the surface membrane of the target cell leading to cell lysis ans death. Also disclosed are microfabrication methods for making such particles and a method of treating cancer patients with such particles.
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