###### Abstract  
Delivering active pharmaceutical agents to disease sites using soft polymeric nanoparticles continues to be a topical area of research. It is becoming increasingly evident that the composition of amphiphilic macromolecules plays a significant role in developing efficient nanoformulations. Branched architectures with asymmetric polymeric arms emanating from a central core junction have provided a pivotal venue to tailor their key parameters. The build-up of miktoarm stars offers vast polymer arm tunability, aiding in the development of macromolecules with adjustable properties, and allows facile inclusion of endogenous stimulus-responsive entities. Miktoarm star-based micelles have been demonstrated to exhibit denser coronae, very low critical micelle concentrations, high drug loading contents, and sustained drug release profiles. With significant advances in chemical methodologies, synthetic articulation of miktoarm polymer architecture, and determination of their structure-property relationships, are now becoming streamlined. This is helping advance their implementation into formulating efficient therapeutic interventions. This review brings into focus the important discoveries in the syntheses of miktoarm stars of varied compositions, their aqueous self-assembly, and contributions their formulations are making in advancing the field of drug delivery. drug delivery; macromolecules; miktoarm polymers; heteroarm star polymers; synthesis; self-assembly; soft nanoparticles; micelles; nanoformulations [color=black]my  
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by avoiding immunogenic response and premature elimination [4]. Using their hydrophobic cores, micelles can load a variety of cargo, including small hydrophobic drugs and biomolecules. A key parameter which is intrinsic to the function of polymeric micelles as drug delivery vehicles is the critical micelle concentration (CMC). At concentrations below their CMC, amphiphilic polymers are disordered. At concentrations at or above the CMC, the continued addition of amphiphiles leads to the formation of their self-assemblies (micelles). Upon administration and introduction into the aqueous biological environment (typically blood), micelles are subject to immense dilution, and low CMCs are required for long circulation times [4; 13]. Micellar drug delivery formulations based on diblock or graft copolymers generally have CMC in a range of \(10^{-4}\)-\(10^{-7}\) M, but are generally more common in the lower end of this range [4; 14; 15; 16; 17]. Another parameter of importance is the micelle size, which is typically expected to be below 200 nm. Given the vasculature and tissue pore sizes, such small diameters can significantly improve micellar circulation and biological distribution, and aid in disease site targeting, due to the EPR effect [10; 11; 12]. One of the more fascinating and advantageous approaches to improving polymer-based drug delivery has come from adjusting the architecture of polymeric backbones. Miktoarm polymers (sometimes known as heteroarm star polymers) are a class of star polymers with asymmetric branching in which at least three branching strands originate from a shared core [18; 19]. Their compositions differ from slight variations in molecular weight, to having completely different repeating units and chemical configurations. Due to their asymmetry, miktoarm variants are categorized in the form: A\({}_{\mathrm{x}}\)B\({}_{\mathrm{y}}\)C\({}_{\mathrm{z}}\), where A, B, and C are examples of polymeric chains, and the subscript denotes their number (Figure 1).