## 5 Conclusions and Future Perspective  
Miktoarm star polymers are beginning to make a significant contribution to advancing the scope of drug delivery using soft polymeric nanoparticles, due to their advantageous properties, compared to the traditionally employed, and most widely studied amphiphilic block copolymers. Advances in the synthesis of miktoarm stars, using high yield methodologies, have facilitated designing formulations with better therapeutic outcomes. Methods, including arm-first and core-first, were initially explored for their syntheses, and were centered around either coupling/grafting pre-synthesized polymeric segments onto a central core, or direct polymerization from a heteromultifunctional core, respectively. These methods individually suffer from drawbacks, such as sterically induced incomplete grafting in arm-first methods, and difficulty in core initiator preparation, as well as polymerization control in core-first methods. Generally, it is best suited to combine these to tailor the overall composition of miktoarm star polymers. One of the most commonly used hydrophilic components in miktoarm stars is poly(ethylene glycol), which is commercially available in varied molecular weights, can be easily functionalized at its ends, and can be covalently linked to core molecules using highly efficient stitching methodologies, including click chemistry and condensation coupling. In-out synthesis, while a viable  
Figure 12: Schematic illustration of the micellar self-assembly of (BA)(AC)2 miktoarm star polymers. Reprinted with permission from reference [65]. Copyright 2016 John Wiley and Sons.  
Figure 13: Independent release of anionic FITC-dextran and cationic rhodamine B from PEG-qPDMAEMA4 micelle/tannic acid-derived microcapsule cores and shells. Reprinted with permission from reference [64]. Copyright 2014 American Chemical Society.  
approach to the construction of miktoarm stars, has not been largely explored in delivering active agents, due to limitations of their self-assembled structures in drug loading in the densely packed cores.  
Due in large part to their unique branching architecture, which can accommodate a variety of task-specific polymer segments, miktoarm star-based self-assemblies are formed at very low CMCs, and show high loading efficiencies, with a sustained drug release. Polymer arm tunability has permitted developing micellar formulations which could target specific organelles or cell receptors, or respond to a variety of autogenous stimuli. The ease with which branching stars can be synthetically articulated continues to offer a platform for the development of multi-stimuli-responsive systems that could deliver drugs with biological cues extra- and intracellularly. It is expected that researchers will continue to design miktoarm constructs possessing polymer segments, which upon self-assembly (i) can switch between micellar cores and coronae, in response to a stimuli, and without structural collapse; (ii) form wrinkled cores, resulting from immiscible core polymer blocks, and increase the number of binding pockets for drug cargo. Considering that noticeable progress has been made in the design and synthesis of miktoarm stars, our understanding of the structure-property relationships of their aqueous self-assembly should continue to be the next focus. This will certainly enhance our efficacy in pharmaceutical interventions in high morbidity rate diseases. Another area of growth is in theranostics, where miktoarm polymers are ideally suited to make a major contribution, due to the ease with which diverse functions, diagnostics, and delivery can be easily introduced via their structural build-up.  
All authors contributed to writing and editing of the manuscript. All authors have read and agreed to the published version of the manuscript.  
This research was funded by Natural Sciences and Engineering Research Council of Canada, grant number RGPIN-2018-05610.  
The authors declare no conflict of interest.