# 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  
#### 3.4.1 Drug Loading Efficiency  
Sinomenine, diltiazem and chlorpromazine were chosen as model detoxification medicines. Figure S2 shows the chemical structures of the three medicines. PS@P(MEO2 MA-_co_-MEO5 MA)-2 nanogels were selected as a carrier to assess drug loading efficiency through the usual physical adsorption method.  
Sinomenine (SIN) (Figure S2A) is a monomer of an effective alkaloid, extracted from the roots of simonenium acutum (a traditional Chinese medicine). Its structure is similar to morphine and is a histamine releasing agent. SIN has anti-inflammatory, antioxidant, analgesic and immunosuppressive effects [32]. Further studies have indicated that SIN can alleviate the symptoms of morphine dependence in rats [33]. In order to improve the clinical efficacy and drug use efficiency of SIN, the SIN must be loaded into a carrier. For example, [PERSON] et al. [34] loaded SIN into the polymer of \(\beta\)-cyclodextrintrim and chitosan, and modified the molecular structure of the polymer by adjusting the monomer concentration and the amount of crosslinker. It was found that the encapsulation efficiency of the SIN in the polymer could be significantly improved.  
Diltiazem (DIZ) (Figure S2B) is a known antagonist of calcium ion, usually used to treat cardiovascular diseases. It was reported that drug addiction can be inhibited by DIZ to some degree [35]. For instance, research shows that DIZ can significantly inhibit the withdrawal reaction and decrease the level of plasma monoamine transmitters in morphine-withdrawing mice [36]. From the point of the inhibitory effect of DIZ on the drug addiction, an effective carrier for DIZ is required. [PERSON] et al. [37] reported that a controlled drug release system of poly(2-hydroxyethyl methacrylate (PHEMA) microgels was effective. The DIZ-loaded PHEMA microgel membrane exhibited a slow release phenomenon within 12 h.  
Chlorpromazine (CPZ) (Figure S2C) is a dopamine-receptor blocker in the central nervous system. CPZ usually has the functions of sedation, tranquility, hypnosis and anesthesia, etc. At the same time, CPZ can block the dopamine receptor in the hypothalamus, disturb endocrine function and accelerate the exudation of pituitary auxin, thus restraining the release of prolactin indirectly. Consequently, CPZ is usually applied in heroin addiction treatment, which can reduce the emergency of the body and finally achieve the goal of detoxification. Recently, some research work has also been devoted to investigating the efficacy, stability and safety of CPZ. For instance, [PERSON] et al. [38] found that the yeast cell wall can be used as capsule material to prepare microcapsules. This CPZ-loaded microcapsule can increase the slow-release and stability of CPZ. [PERSON] et al. [39] used a copolymer of poly(lactic acid-_co_-glycolic acid) (PLGA) as a carrier to load CPZ, and found that higher entrapment efficiency and drug loading could be obtained by adjusting the concentration of CPZ, PLGA, polyvinyl alcohol and so on.  
The encapsulation efficiency of PS@P(MEO2 MA-_co_-MEO5 MA)-2 nanogels was determined to be 74.33%, 77.6% and 70.70% for SIN, DIZ and CPZ, respectively. Moreover, the encapsulation efficiency of pure PS core was determined to be 78.5%, 79.03% and 80.4%, for SIN, DIZ and CPZ, respectively, which is close to that of PS@P(MEO2 MA-_co_-MEO5 MA)-2 nanogels. These results suggest that the loading of the three detoxification medicines is mainly borne by the PS core in PS@P(MEO2 MA-_co_-MEO5 MA)-2 nanogels. The three detoxification medication molecules passed through the P(MEO2 MA-_co_-MEO5 MA)-2 shell into the PS core. This is because heterocyclic aromatic groups of detoxification medication molecules and hydrophobic network chain in the PS core may form intermolecular complexes by means of a hydrophobic interaction.