Asymmetric AB₃ Miktoarm Star Polymers: Synthesis, Self‐Assembly, and Study of Micelle Stability Using AF₄ for Efficient Drug Delivery

Abstract

A simple and versatile methodology, which employs a combination of ring-opening polymerization and alkyne-azide click chemistry to synthesize amphiphilic AB3 miktoarm stars, is reported. Their aqueous self-assembly behavior was studied using dynamic light scattering, fluorescence, and asymmetrical flow field-flow fractionation (AF4). AB3 miktoarm stars form micelles which incorporate curcumin with high efficiency, and significantly reduce the viability of glioblastoma cells in spheroids. We demonstrate that AF4 is an effective technique to determine the size distribution of self-assembled structures exposed to a biological medium. The ease, with which asymmetric AB3 miktoarm polymers are constructed, provides a platform that can be widely employed to deliver a variety of lipophilic drugs.

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

“…Polymeric carriers have the potential to improve the stability and solubility of curcumin [60][61][62]. Our research group has previously reported the incorporation of curcumin into A2B star polymer micelles and effectiveness of this preparation in glioblastoma [63,64]. A retention of curcumin's biological activity in nanocarriers, an enhanced permeability and retention (EPR) effect and diffusion of curcumin into the neighboring glioblastoma cells could provide an improved therapeutic intervention in vivo [65] Pyrrolidine-2 is an inhibitor of cPLA2a, a key rate limiting enzyme in the synthesis of eicosanoids and a necessary player in the formation of lipid droplets [66,67].…”

Miktoarm Star Polymers: Branched Architectures in Drug Delivery

“…For example, in an AB 2 polymer where B segments are added by click chemistry, the relative integrations of B-derived protons become double, compared to those from the A segment. Analysis of its GPC chromatogram showed a unimodal peak, implying that there are no unconjugated segments [ 24 , 38 , 46 , 53 , 55 ].…”

“…Micellar drug retention has generally been associated with more sustained drug release and dampening burst release [ 32 , 48 , 55 , 70 ], which has the benefit of increasing drug bioavailability. This could be the result of strong interactions and more sites of association between the encapsulated drug and multiple hydrophobic chains [ 27 , 52 , 70 , 133 ].…”

Telodendrimer-Based Macromolecular Drug Design using 1,3-Dipolar Cycloaddition for Applications in Biology

“…This suggests that the telodendrimer assumes a hydrophobic core/hydrophilic corona type structure in D2O. We examined similar self-assembly of the telodendrimer using an acetone/water co-solvent evaporation method [34][35][36]. The resulting assemblies were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM) ( Figure 3).…”