## 6 Impact of Multi-Arm Topology on PCL-Based Polymer Properties for Drug Delivery
The self-assembly of these miktoarms exhibited a very low CMC, indicating high colloidal stability in aqueous solution. MTX was used as a model drug with low solubility. The micelles showed high drug loading capacity, and 26% of the drug was released in simulated gastric fluid (SGF, pH 1.2) over 48 h, whereas the maximum drug release was 98% in simulated intestinal fluid (SIF, pH 7.4). Therefore, pH-sensitive micelles can be used as an effective carrier for the oral administration of hydrophobic drugs with prolonged and controlled release. In the study by [PERSON] et al. [165], another multi-arm structure was described in detail and named toothbrush-type amphiphilic copolymer. This structure was based on PEG and PCL chains, where the number of PCL arms was represented by n in the formula PEG-b-(HEMA-g-PCL)\({}_{n}\). These polymers were synthesized using a combination of ATRP and ROP, in which the macromolecular initiator of PEG-b-PHEMA initiated the ring opening of \(\epsilon\)-caprolactone (CL). This multi-arm structure exhibited very different thermal characteristics compared to its linear counterpart. Furthermore, the increase in the number of PCL arms further reduced the crystallization temperature T\({}_{c\text{PCL}}\) of the toothbrush-type copolymer to a remarkably low value (\(-17.4\)\({}^{\circ}\)C). These results suggest that the crystallization properties of these PEG-b-(PHEMA-g-PCL) toothbrush-type copolymers can be easily adjusted depending on the number and length of the PCL segments (Figure 10). The group also showed that these modifications of physical properties have an impact on assembly and encapsulation properties. Due to the difficulty of recrystallizing the short and grafted branches of PCL under administration conditions, the micelles prepared from these toothbrush-shaped copolymers exhibited a higher loading capacity for DOX than the micelles formed by the linear polymer PEG-b-PCL. DOX-loaded toothbrush-shaped copolymer micelles also demonstrated exceptional stability in aqueous solution compared to DOX-loaded linear PEG-b-PCL polymer micelles. The in vitro release of DOX from brush-shaped copolymer micelles was faster than that of linear sequenced copolymer micelles. In addition, the studies revealed that DOX-loaded brush-shaped copolymer micelles could be effectively internalized by EJ bladder carcinoma cells and that DOX could be released in endocytic compartments and reach the nucleus. The brush-shaped copolymer micelles based on PEG and PCL, which have enhanced properties compared to those of linear PEG-b-PCL, can serve as versatile nanocarriers for a range of lipophilic drugs. Figure 9: Synthesis of AB\({}_{3}\)-type multi-arm polymers based on PCL-PEG. Another work conducted by [PERSON] [186] utilized a simple and effective combination of ROP, SA ATRC (styrenics-assisted atom transfer radical coupling), and ATRP to synthesize PCL-based \(\upmu\)-star copolymers. The PCL-\(\upmu\)-PSt and PCL-\(\upmu\)-PtBA copolymers exhibited highly satisfactory physical characteristics. Additionally, the \(\mathrm{T_{g}}\) of the amorphous segment and the \(\mathrm{T_{m}}\) of the PCL segment were detected in both \(\upmu\)-star copolymers during the first DSC analysis, indicating the presence of semi-crystalline PCL. However, the \(\mathrm{T_{m}}\) of PCL disappeared during the second scan, resulting from the restricted chain mobility of these polymers. Furthermore, a multistep degradation profile was detected, which was attributed to subsequent degradations of different arm analogues. The morphology of pure PCL demonstrated obvious heterogeneity due to the amorphous and crystalline macrophases, allowing these PCL-\(\upmu\)-PSt and PCL-\(\upmu\)-PtBA copolymers to form interesting nanoparticles with an average diameter of approximately 250 and 45 nm, respectively. The authors then performed a deprotection of the tert-butyl group from the PCL-\(\upmu\)-PtBA copolymer, and their studies showed a flat and smooth surface, which was due to the good miscibility of PCL and PAA segments.