# Biomedical Application of Cyclodextrin Polymers Cross-Linked via Dianhydrides of carboxylic Acids
## 4 Biomedical Applications
### Simple Oral Complex Drug-NS-PMDA  
Meloxicam (Figure 1) is a painkiller and anti-inflammatory drug. [PERSON] et al. decided to encapsulate this drug in NS cross-linked via PMDA, due to its limited solubility in water and the instability. To determine bioavailability, they studied the degree and the rate of solubility and drug stability in vitro and in vivo [37]. In addition, analgesic and anti-inflammatory activities were tested. Drug release tests with NS demonstrated controlled release of the substance for 24 h. The solubility of the drug increased significantly, and its rate decreased with less crystallinity degree of meloxicam. The complex was stored for three months, and subsequent characterization confirmed the absence of any significant changes in the drug release, particle size, and the efficiency of encapsulation. The last tests have indicated the increase in the analgesic and anti-inflammatory activities of the meloxicam-NS system in relation to the drug itself. Therefore, this type of polymer is considered a promising and interesting meloxicam carrier [37]. Later, in 2016, [PERSON]'s group invented and tested nanosuspensions formed from the complexation of lansoprazole (Figure 2), a proton pump inhibitor used in the treatment of gastric ulcer, gastroesophageal reflux disease, and Zollinger-Ellison syndrome. The group carried out tests on solubility, chemical stability, and in vitro drug release to assess the effect of the NS. In comparison to the pure drug and the complex drug-NS, a significant improvement of solubility of over 40% was noted. Increased stability resulted in increased protection against acid degradation in the stomach. Additionally, in vitro studies have demonstrated the controlled release of lansoprazole, which is much more satisfactory than the release of pure drug. Lansoprazole in NS can be considered as a promising method in the treatment of gastric ulcers [38]. Rosuvastatin (Figure 3) prevents high-risk cardiovascular disease by inhibiting cholesterol biosynthesis. The basic limitation leads to low bioavailability of about 20% because of the poor solubility of the drug. [PERSON]'s team, in 2018 complexed rosuvastatin in CD-NS by lyophilization and then tested the in vitro drug release, pharmacokinetics, and bioavailability. The same tests  
Figure 1: Structure of meloxicam. Figure 2: Structure of lansoprazole. were carried out with a commercial rosuvastatin, rosuvastatin suspension, and the results were compared. Pharmacokine studies of the complex have indicated the increased absorption and higher concentration of the drug over a long period of time compared to the other tests (rosuvastatin without a complex). Thus, the data showed an increase in the oral bioavailability of the drug NS complex, which is a promising alternative to the commercial drug [39]. In the case of HIV treatment by rilpivirine (Figure 4), basic problems include poor solubility and dissolution rate that results in low bioavailability (32%) [40]. Due to this fact, research on the improvement of bioavailability via PMDA-NS was undertaken by [PERSON] et al., 2018. In addition, the ternary complex was formed with drug-NS by adding tocopherol polyethylene glycol succinate. Based on the results of in vitro solubility and in vivo pharmacokinetics in rats, a two-fold increase in the bioavailability for binary and ternary complexes was discovered [40]. Similar studies were carried out on the PMDA-NS complex with curcumin (Figure 5) by [PERSON] and colleagues in 2018. The drug has a potential anticancer effect, but also low solubility and photostability. The effect of complexing was studied carefully. Changes in the solubility, the release rate of the active substance, photodegradation, and cytotoxicity were analyzed. The first test indicated a significant improvement in water solubility. The second test showed a 16-fold increase of in vitro release in comparison to the pure curcumin. Besides this, the photostability of curcumin was also found to have improved significantly by up to 1.7 times.