Figure 2.1.3 TPGS concentration and Paclitaxel solubility are directly related. Figure created by M. Varma, 200522.
TPGS has been incorporated into various drug formulations partly because of its ability to overcome multidrug resistance (MDR). By inhibiting P-glycoprotein (P-gp) activity, the relative cytotoxicity of drugs such as doxorubicin, vinblastine, and paclitaxel was increased19. P-gp is a drug efflux pump, a.k.a. multidrug resistance protein 1 (MDR1), located in the cell membranes of distinct tissues throughout the body that transports a wide range of molecules in an out of the cells. The pump is ATP-dependent and prevents accumulation of multiple anticancer drugs inside targeted cells. Certain cancer cells will develop additional …show more content…
(A) Absorption into cells. (B) Secretion from cells. Figure created by Collnot et al., …show more content…
The benefit of using micelles as DDS is to increase the blood circulation time, which in the cases of NK91125 and SP1049C26 were by a factor of 3 in comparison to the free drug. Issues surrounding the utilization of more micelle formulations include insufficient drug loading, stability, and selective uptake by targeted cells17. A common misconception is that micelles are not solid structures or necessarily circular. Micelles exist in an active equilibrium with other surfactant molecules where monomers switch between adsorbing at the air-liquid interface, moving freely throughout the bulk solution, and aggregating to form micelles17. Below the CMC, monomers remain free in solution and adsorbing at the air-liquid interface. As the concentration of monomers increases, the interfacial free energy, a.k.a. surface tension, is reduced. The CMC is reached when the solution and interface are saturated with individual monomers. The addition of any subsequent monomers results in the formation of micelles17. Surface tension is one method to measure and determine the CMC of surfactant solutions. As more monomers adsorb at the air-liquid interface the surface tension is lowered until the concentration where micellization occurs (Figure 2.1.5). There are various ways to experimentally determine the CMC. All methods rely on the physiological changes that occur above the CMC. Accurately
TPGS has been incorporated into various drug formulations partly because of its ability to overcome multidrug resistance (MDR). By inhibiting P-glycoprotein (P-gp) activity, the relative cytotoxicity of drugs such as doxorubicin, vinblastine, and paclitaxel was increased19. P-gp is a drug efflux pump, a.k.a. multidrug resistance protein 1 (MDR1), located in the cell membranes of distinct tissues throughout the body that transports a wide range of molecules in an out of the cells. The pump is ATP-dependent and prevents accumulation of multiple anticancer drugs inside targeted cells. Certain cancer cells will develop additional …show more content…
(A) Absorption into cells. (B) Secretion from cells. Figure created by Collnot et al., …show more content…
The benefit of using micelles as DDS is to increase the blood circulation time, which in the cases of NK91125 and SP1049C26 were by a factor of 3 in comparison to the free drug. Issues surrounding the utilization of more micelle formulations include insufficient drug loading, stability, and selective uptake by targeted cells17. A common misconception is that micelles are not solid structures or necessarily circular. Micelles exist in an active equilibrium with other surfactant molecules where monomers switch between adsorbing at the air-liquid interface, moving freely throughout the bulk solution, and aggregating to form micelles17. Below the CMC, monomers remain free in solution and adsorbing at the air-liquid interface. As the concentration of monomers increases, the interfacial free energy, a.k.a. surface tension, is reduced. The CMC is reached when the solution and interface are saturated with individual monomers. The addition of any subsequent monomers results in the formation of micelles17. Surface tension is one method to measure and determine the CMC of surfactant solutions. As more monomers adsorb at the air-liquid interface the surface tension is lowered until the concentration where micellization occurs (Figure 2.1.5). There are various ways to experimentally determine the CMC. All methods rely on the physiological changes that occur above the CMC. Accurately