## 4 Application of PCL-Based Materials in Nanoformulations
### Hydrogels  
Hydrogels are three-dimensional networks of hydrophilic polymer chains that can swell in hydrophilic environments without losing their structure and cannot dissolve in organic and inorganic solvents due to the presence of cross-linking between the polymer chains. From a rheological point of view, hydrogels exhibit viscoelastic behavior and partially purely elastic behavior [40]. In another aspect, the hydrogel has a very porous structure that permits substrates to be loaded into the gel framework and released at a rate that depends on the diffusion coefficient of the substrate through the gel network. In this concept different types of PCL-based multi-arm copolymers have been synthesized and used as physical hydrogels with different thermosensitive characteristics.  
Multi-arm copolymers have been synthesized mainly by using a diol-initiated method such as PEG (with different numbers of arms). In this case, multi-block PEG/PCL copolymers with 3, 4, and 8 arms were synthesized using this method. At a certain concentration of the copolymer in the aqueous solution, the number of aggregates increases, and the volumetric fraction of the aggregates exceeds the maximum packing fraction, which leads to gelation of the system. Research has shown that the solubility of multi-arm copolymers in an aqueous medium is higher than that of linear polymers with the same hydrophobic/hydrophilic ratio. Additionally, PCL-based multi-arm copolymers form homogeneous and transparent hydrogels, whereas hydrogels formed from linear copolymers are generally white, opaque, and brittle, reducing their consistency during handling and limiting their applications in the field of encapsulation [97]. What is more impressive is that an increase in the number of PCL arms in the copolymers facilitates the aggregation and inter-aggregation of the bridges, thus facilitating the formation of the hydrogel [98].  
The structure of PCL-based copolymers can influence the properties of the gel formed. PEG/PCL copolymers can be formed by an ester linkage between the PEG and PCL chains (PEG-OCO-PCL). The work of [PERSON] and colleagues [99], who synthesized PEG-PCL copolymers with an amide bond between the chains (PEG-NHCO-PCL), showed that PEG-NHCO-PCL hydrogels exhibited a higher storage modulus (13 Kpa) than conventional hydrogels that contain ester bonds between the PEG-OCO-PCL chains (1.6 Kpa). This is due to the restricted conformational freedom of the amide groups, which leads to more effective physical cross-linking with a more rigid structure. In addition, interactions between the amide groups have caused an increase in the density of cross-linking and have improved the mechanical properties. In vitro studies have shown that the hydrolysis of PEG-OCO-PCL generally occurs at the ester linkages between PEG and PCL, resulting in a decrease in the hydrophobic chains of PCL and a disruption of the network structure. On the other hand, the amide groups in PEG-NHCO-PCL have been found to be more stable, and hydrolysis only occurs at the ester groups in the PCL chains. Thus, hydrogels formed from PEG-NHCO-PCL copolymers have greater in vitro stability (up to 16 days) than PEG-OCO-PCL hydrogels.  
Despite these advantages, hydrogels have several limitations. Significant swelling of the hydrogel in aqueous environments leads to the formation of materials with poor mechanical properties that limit their use in load-bearing applications. Hydrophobic substrates such as drugs cannot be applied to hydrogels due to the thermodynamic incompatibility between the hydrophilic chain, water, and the hydrophobic drug.