# Automatic Detoxification Medicine Delivery by Thermo-Sensitive Poly(ethylene glycol)-Based Nanogels
## 4 Conclusions  
Well-defined core-shell structured PS@P(MEO\({}_{2}\)MA-co-MEO\({}_{5}\)MA) nanogels have been successfully synthesized through the preparation of a hydrophobic PS core, together with the immobilization of a thermo-sensitive nonlinear poly(ethylene glycol)-based copolymer P(MEO\({}_{2}\)MA-co-MEO\({}_{5}\)MA) shell on PS core microspheres. The inner hydrophobic PS core microspheres can provide high loading capabilities for hydrophobic sinomemine, diltiazem and chlorpromazine. The thermo-sensitive outer nonlinear poly(ethylene glycol)-based copolymer P(MEO\({}_{2}\)MA-co-MEO\({}_{5}\)MA) shell consisted of an initial monomer feeding molar ratio \(n\)(MEO\({}_{2}\)MA)/\(n\)(MEO\({}_{5}\)MA) of 1:3 and the matching feeding amounts, e.g., MEO\({}_{2}\)MA (0.25-0.5 mmol) and MEO\({}_{5}\)MA (0.75-1.5 mmol) in 100 mL of 0.227 g L\({}^{-1}\) PS dispersion. This optimum designed shell layer can provide good biocompatibility within a certain concentration range (<50 \(\mu\)g mL\({}^{-1}\)), excellent stability in aqueous media, and thermally regulated drug release in the temperature fluctuations during drug addiction. Moreover, the obtained sinomemine-, diltiazem- and chlorpromazine-loaded PS@P(MEO\({}_{2}\)MA-co-MEO\({}_{5}\)MA) nanogels showed obvious in vitro thermo-sensitive and sustained-release characteristics up to 70 h. The PS@P(MEO\({}_{2}\)MA-co-MEO\({}_{5}\)MA) nanogels designed by the rational integration of a drug-loaded PS core and thermo-sensitive nonlinear poly(ethylene glycol)-based copolymer shell should offer broad opportunities to effectively improve the utilization rate and reduce the side effects of detoxification medicines.  
The following supporting information can be downloaded at: [[https://www.mdpi.com/article/10.3390/polym14050892/s1](https://www.mdpi.com/article/10.3390/polym14050892/s1)]([https://www.mdpi.com/article/10.3390/polym14050892/s1](https://www.mdpi.com/article/10.3390/polym14050892/s1)), Figure S1: Boltzmann fitting-differential curves dependent on temperature-\(R_{\rm h}\) values of (A) PS@P(MEO\({}_{2}\)MA-co-MEO\({}_{5}\)MA)-1, (B) PS@P(MEO\({}_{2}\)MA-co-MEO\({}_{5}\)MA)-2, and (C) PS@P(MEO\({}_{2}\)MA-co-MEO\({}_{5}\)MA)-3 nanogels prepared with the same \(n\)(MEO\({}_{2}\)MA) /\(n\)(MEO\({}_{5}\)MA) feeding molar ratio of 1:3 but different initial monomer (MEO\({}_{2}\)MA and MEO\({}_{5}\)MA) amounts of shell in 100 mL of 0.227 g L\({}^{-1}\) PS dispersion; Figure S2. Chemical structures of (A) sinomemine, (B) diltiazem and (C) chlorpromazine.  
Conceptualization, J.S. and X.Z.; methodology, T.F.; formal analysis, T.F. and Y.M.; investigation, T.F., Y.M. and Y.Z.; resources, J.W.; data curation, T.F. and T.W.; writing--original draft preparation, T.W. and J.S.; writing--review and editing, S.W.; visualization, T.F. and T.W.; supervision, T.W. and J.S.; funding acquisition, J.S., T.W., X.Z. and J.W. All authors have read and agreed to the published version of the manuscript.  
This research was funded by the National Natural Science Foundation of China, grant number 21564018, 21363029, 21965039 and 22165034.  
Not applicable.  
The data presented in this study are available on request from the corresponding author.  
The authors declare no conflict of interest.