**5.2 Last generations of NSs for selected target drug delivery**

Stimuli-responsive NSs represent the third generation, polymers that have been designed to modulate their behavior according to the surrounding environment. In this case, changes in the chemical structure of the material were reported to be triggered by pH, temperature gradients, or oxidative/reducing conditions. This feature was exploited for studying the targeted release of drugs, changes in color, and permeability. The use of glutathione (GSH) bioresponsive CD-NS was proposed as the system to deliver anticancer drugs or bioactive compounds [80–83]. This is because GSH is 100 to 1000 times higher inside cells than that in the extracellular fluids and circulation. Indeed, in cancer cells, this concentration is almost higher being a good system for target drug delivery [84]. Different drugs such as doxorubicin [81] or bioactive compounds such as resveratrol [82] were tested showing a well-targeted drug delivery, and therefore is considered a promising therapy. In addition, the linkage of cholesterol was proposed as a good procedure for increase the targeted drug delivery of doxorubicin-loaded CD-NS [85].

Lastly, molecularly imprinted cyclodextrin-based polymers (**Figure 3**) define the fourth generation of NSs. Molecular imprinting represents a specific approach of inducing molecular recognition features to a three-dimensional polymer. This property can be achieved as a result of the presence of a template molecule introduced during synthesis. The template molecule after being removed from the polymer matrix leaves size-complementary vacancies, enabling the network to display high selectivity and affinity toward the chosen template. Eventually, molecularly

**Figure 3.**

*Schematic synthesis of molecularly imprinted NSs.*


*Strategies to Develop Cyclodextrin-Based Nanosponges for Smart Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.100182*


β*CD, Beta Cyclodextrin;* ϒ*CD, Gama Cyclodextrin; HDI, Hexamethylene diisocyanate; CDI, Carbonyldiimidazole; DMC, Dimethyl Carbonate; DPC, Diphenyl carbonate; PMDA, Pyromellitic Dianhydride.*

#### **Table 2.**

*The use of cyclodextrin based nanosponges in drug delivery.*

imprinted CD-NSs are studied as suitable material to develop biosensors, drug delivery systems, catalysts, or synthetic antibody mimics [86–88]. A good example of this application is the L-Dopa as a novel possibility to treat Parkinson's Disease. The molecularly imprinted CD-NSs showed a slower and more prolonged release profile than the non-imprinted NSs, indicating the good capacity to better complex L-Dopa than non-imprinted NS. The use of CDs in controlled and targeted drug delivery is shown in **Table 2**.
