## 6 Impact of Multi-Arm Topology on PCL-Based Polymer Properties for Drug Delivery
(2012) demonstrated this by synthesizing new sequenced copolymers using a dichloro-polyester, which was initially synthesized through the ROP of PCL, as a macroinitiator for GMA polymerization by ATRP (Figure 7). The combination of these two processes yielded well-defined copolymers across a broad range of compositions. It was discovered that the PCL:PGMA ratios exerted a significant influence on the properties of the copolymers, particularly their micellization properties. These sequenced copolymers self-assembled into various morphologies, such as normal spherical micelles, vesicles, and lamellae. Moreover, it was observed that the copolymer composition and its concentration in THF significantly impacted the aggregate morphologies. Figure 6: The AB\({}_{2}\)-type mikotarm copolymer (PEG-PCL\({}_{2}\)) synthesized using a “core-first” strategy (**a**,**b**); Linear PEG-b-PCL diblock copolymers synthesize (**c**) (Adapted from [181]). Figure 7: Synthesis of multiarms (PCL-PGMA) through the ROP and ATRP. Through a three-step reaction sequence [183], a multi-functional initiator has been synthesized which has one initiation site for ROP and two initiation sites for ATRP. Initially, the initiator was used for the ROP reaction of caprolactone that yielded a polymer with secondary bromide end groups. Later, the polycaprolactone produced was used as a macroinitiator to carry out ATRP of tert-butyl acrylate (tBA) or methyl methacrylate (MMA), which resulted in the formation of A\({}_{2}\)B-type star polymers (Figure 8). The multi-armed polymers developed in this study exhibited a single transition temperature similar to that of the PMMA or PtBA homopolymers, likely due to the relatively short length of the PCL chains compared to those of PMMA and PtBA. As a result, the thermal transitions of the copolymers are dominated by the longer PMMA or PtBA chains. Although this reduces the thermal character of the PCL, it was observed that molecular weights are controlled with low polydispersity (weight-average molecular weight/number-average molecular weight ratio of 1.23) thanks to the ROP-ATRP sequence. This offers the possibility to modify the thermal behavior by altering the length of the PCL chains relative to those of PtBA or PMMA. Other topologies, such as the AB\({}_{3}\) structure, have benefited from the advantages of the AB\({}_{2}\) and A\({}_{2}\)B structures. In 2015, a team led by [PERSON] [184] presented a simple method for synthesizing AB\({}_{3}\)-type multi-arm polymers with one PCL arm and three PEG arms of varying chain lengths (Figure 9). The method combines ring-opening polymerization and alkyne-azide click chemistry. These AB\({}_{3}\) miktoarm stars form micelles that efficiently incorporate curcumin, leading to a significant reduction in glioblastoma cell viability in spheroids. Asymmetric AB\({}_{3}\) multi-arm polymers are easy to construct, providing a versatile structure for delivering various lipophilic drugs. Although oral drug delivery systems (DDS) based on amphiphilic linear polymers that form micelles have been extensively studied in recent years for poorly water-soluble drugs, several of them have not shown satisfactory performance, such as high critical micelle concentration (CMC), low loading efficiency, and uncontrollable drug release, which may lead to severe toxicity to normal cells due to high local drug concentration. This has driven the development of a new polymer design with a reasonable structure that could be an effective means to increase release efficiency. Figure 8: Schematic synthesis of A\({}_{2}\)B-type star polymers based on PCL-PtBA. In this concept, [PERSON] et al. [185] explored a new pH-sensitive multi-arm sequenced copolymer for the delivery of hydrophobic drugs to improve the performance of the support for oral DDS. This group prepared new pH-sensitive micelles from a multi-arm miktoarm star sequenced copolymer, mPEG-bP(MMA-co-MAA)\({}_{2}\), via an ATRP technique and dialysis method.