Interactions Of Polymeric Micelles With Cancer Cells

Once the drug-loaded micelles have reached the tumor site, there are several mechanisms that have been proposed for the delivery of micelle-incorporated drugs into the cancer cells as

FIGURE 17.4 Proposed mechanisms for the delivery of micelle-formulated drugs into cancer cells. (a) Drug is released from the micelles and diffused into the cell as free drug. (b) The drug-loaded micelles diassemble in the extracellular space and release the drug; the released drug then diffuses across the cell membrane into the intracellular space. (c) Intact drug-loaded micelles are internalized via adsorptive pinocytosis after adsorption onto the cell surface or (d) by fluid-phase endocytosis. The internalized drug-loaded micelles eventually reach the lysosome where the drug can be released (e) by diffusion or (f) following disassembly or degradation of the micelles.

FIGURE 17.4 Proposed mechanisms for the delivery of micelle-formulated drugs into cancer cells. (a) Drug is released from the micelles and diffused into the cell as free drug. (b) The drug-loaded micelles diassemble in the extracellular space and release the drug; the released drug then diffuses across the cell membrane into the intracellular space. (c) Intact drug-loaded micelles are internalized via adsorptive pinocytosis after adsorption onto the cell surface or (d) by fluid-phase endocytosis. The internalized drug-loaded micelles eventually reach the lysosome where the drug can be released (e) by diffusion or (f) following disassembly or degradation of the micelles.

illustrated in Figure 17.4.103-106 In general, drugs can enter the cells via diffusion as free molecules following release from the micelles (Figure 17.4a and b) or be internalized as drug molecules entrapped within the micelles (Figure 17.4c-f). In addition, certain block copolymers have also been found to act as chemosensitizers or modulators of drug efflux pumps.26,34,107-111

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