# Automatic Detoxification Medicine Delivery by Thermo-Sensitive Poly(ethylene glycol)-Based Nanogels
## 3 Results and Discussion
### Drug Loading and In Vitro Thermo-Sensitive Regulated Drug Release
#### 3.4.2 In Vitro Release Studies  
The cumulative release profiles of SIN, DIZ and CPZ from the PS@P(MEO2 MA-_co_-MEO5 MA)-2 nanogels are shown in Figure 6. The in vitro release studies were carried out in a buffer solution to avoid the decomposition of SIN, DIZ and CPZ in water over a long period of time. As can be seen in the curves (\(\square\)) of Figure 6A-C, three blank releaseexperiments of free SIN, DIZ and CPZ solutions with the equivalent amount of SIN, DIZ and CPZ loaded in the PS@P(MEO\({}_{2}\)MA-_co_-MEO\({}_{5}\)MA)-2 nanogels, respectively, were carried out under the same conditions at 38 \({}^{\circ}\)C. These curves of blank release exhibited a very rapid release in a few minutes, which shows that the role of dialysis membrane is ignorable in the release process. It is clear that if we compare these release curves between the 22 \({}^{\circ}\)C and 38 \({}^{\circ}\)C in Figure 6A-C, the distinct differences can be observed. With the prolongation of release time, the cumulative release rates of the three samples at 38 \({}^{\circ}\)C are higher than that at 22 \({}^{\circ}\)C, indicating that this PS@P(MEO\({}_{2}\)MA-_co_-MEO\({}_{5}\)MA)-2 nanogel has significant thermosensitive release characteristics. The results can be attributed to the thermo-sensitive shell. When the ambient temperature increases, the P(MEO\({}_{2}\)MA-_co_-MEO\({}_{5}\)MA) shrinks. This shrinkage further compresses the PS core, squeezing out the drug molecules. Furthermore, a sustained-release phenomenon can also be observed in Figure 6A-C. For example, the cumulative release rates of the PS@P(MEO\({}_{2}\)MA-_co_-MEO\({}_{5}\)MA)-2 nanogels reached 98.0%, 90.3% and 95.0% for SIN, DIZ and CPZ, respectively, at 38 \({}^{\circ}\)C in 70 h, indicating that the SIN-, DIZ- and CPZ-loaded PS@P(MEO\({}_{2}\)MA-_co_-MEO\({}_{5}\)MA)-2 nanogels can provide a sustained release of detoxification medicines. This is probably due to the slow diffusion of the three detoxification medication molecules from the PS cores of nanogels to the P(MEO\({}_{2}\)MA-_co_-MEO\({}_{5}\)MA) shell layer, and then slowly spreading from the shell layer to the buffer solution. This sustained-release effect is very important for the utilization of drugs, especially for the stability and safety of detoxification medicines. One foreseeable prospect is that the drug-loaded nanogels can be used as an oral drug. When the nanogels are made into an oral liquid, it may enter the body through adsorption in the stomach or intestines. When drug addicts are addicted to drugs, their body temperature rises, and the drug-loaded nanogels can automatically release the drug that has been loaded. It may be a sustained release process. The automatic release of the drug can alleviate the dependence of the human body on drugs.  
Figure 6: Cumulative release of (**A**) SIN-, (**B**) DIZ- and (**C**) CPZ-loaded PS@P(MEO\({}_{2}\)MA-_co_-MEO\({}_{5}\)MA)-2 in buffer solution at both 22 \({}^{\circ}\)C (\(\blacksquare\)) and 38 \({}^{\circ}\)C (\(\bullet\)) under different times. In the blank (\(\square\)), a diluted solution of free detoxification medicines with the same amount of medicines loaded in PS@P(MEO\({}_{2}\)MA-_co_-MEO\({}_{5}\)MA)-2 was performed at 38 \({}^{\circ}\)C.