## 7 The Key Parameters of Self-Assembly in Multi-Arm Polymers
### Solvophobic/Solvophilic Balance
In addition, the effectiveness of the encapsulation and the controlled release profile are directly affected by the size, morphology, and interactions of the copolymer blocks [194]. This is due to the polymer's ability to interact with the drug through various mechanisms such as hydrophobic interactions, \(\pi\)-\(\pi\) interactions, and hydrogen bonding. When choosing a polymer for the core, it is important to ensure that the polymer is compatible with the drug being delivered. Polymers can be carefully selected based on their chemical properties and functional groups to optimize their interactions with the drug. For example, hydrophobic polymers could improve the solubilization of hydrophobic drugs by forming micelles in aqueous media. In addition, the length of the hydrophobic polymers could also affect the critical micelle concentration (CMC) of the carrier. Increasing the hydrophobic polymer length could decrease the CMC, which can highly enhance drug solubilization and loading capacity [195]. However, it is important to balance the hydrophilic and hydrophobic content of the polymer to ensure that the carrier remains stable in aqueous media. If the hydrophobic domains are too large, the micelle may have a larger core, which can lead to instability and aggregation. In order to achieve the desired drug delivery performance, it is important to meticulously optimize the selection of the polymer and its chemical composition. In 2013, [PERSON] and et al. [196] synthesized a series of novel amphiphilic copolymers, including hydrophilic PEG blocks and hydrophobic PCL blocks. These multi-arm amphiphilic copolymers, which mimic the structural properties of phospholipids and have high potential domains, are capable of forming nanostructures and serving as effective drug delivery systems. DOX was chosen as a model drug to be loaded into the PEG-PCL multi-arm nanocariers, and the in vitro release profiles of these DOX-loaded nanocariers showed sustained release patterns. Additionally, PEG-PCL\({}_{2}\) nanocarriers showed better cellular uptake. The authors of this study have shown that the length of the PCL arms directly influences the properties of the nanocariers and that multiarms self-assembled into spherical micelles in aqueous solution when the length of the PCL blocks decreased. Similarly, a lamellar micellar structure was observed when the length of the PCL blocks increased. In 2010, a report was published on a series of copolymers composed of (PEG)\({}_{2}\)-PCL\({}_{n}\), where the value of n ranged from 3000 to 19,000 [197]. The micelles formed by (PEG\({}_{775}\))\({}_{2}\)-PCL\({}_{19000}\) had the largest hydrodynamic radius Rh, which was expected due to the longer PCL chain leading to a larger core. Additionally, this copolymer has demonstrated the lowest CMC and highest encapsulation rates. Linear diblock copolymers, PEG\({}_{2000}\)-PCL\({}_{5800}\) and (PEG\({}_{775}\))\({}_{2}\)-PCL\({}_{5800}\), were also created, and it was discovered that the multi-arm structures resulted in smaller-sized micelles. Similarly, [PERSON]'s [198] development of multi-arm polymers in aqueous solution resulted in exceptionally low CMC values (ranging from 0.0029 to 0.0035 mg mL\({}^{-1}\)), which suggests that the micelles have a high degree of stability in solution. The micelles, whether blank or containing doxorubicin (DOX), were able to self-assemble into spherical shapes with average sizes between 110 to 240 nm, depending on the copolymer architecture. These findings, as well as others, clearly illustrate the significant impact of polymer composition on micelles properties. Figure 15: The effect of increasing the chain length on the nanoencapsulation parameters; for PCL(PCL-b-PEG)\({}_{3}\) (**A**), and in the case (PEG)\({}_{2}\)-PCL (**B**). On the other hand, [PERSON] et al. [199] have produced poly(ethylene glycol)-b-polyacrylic acid-b-polycaprolactone (mPEG-b-PAA-b-PCL) terpolymers with multiple arms that are sensitive to pH.