Synthesis, Characterization And Self-Assembly Study Of Amphiphilic Star Polymers Based On Resorcinarene

Well-defined amphiphilic A8B4miktoarm star copolymers containing eight poly(ethylene glycol) arms and four poly(ε-caprolactone) arms (R-8PEG-4PCL) were prepared by a combination of "click" reaction strategy and controlled ring-opening polymerization (CROP). First, multifunctional precursor (R-8N3-4OH) with eight azides and four hydroxyls was synthesized by the derivatization of resorcinarene. Then eight-PEG-arm star polymer (R-8PEG-4OH) was synthesized through "click" reaction of R-8N3-4OH with presynthesized alkyne-terminated monomethyl PEG (mPEG-A) in the presence of CuBr/N,N,N’,N",N"’-pentamethyldiethylenetriamine (PMDETA) in toluene. Finally, R-8PEG-4OH was used as tetrafunctional macroinitiator to prepare resorcinarene-centered A8B4miktoarm star copolymers via CROP of ε-caprolactone utilizing Sn(Oct)2as catalyst at100℃. These miktoarm star copolymers could self-assemble into spherical micelles in aqueous solution with resorcinarene moieties on the hydrophobic/hydrophilic interface.Eight-arm resorcinarene-centered poly(ε-caprolactone)-block-poly(ethylene glycol)s (SPCL-b-PEG) have been prepared by a combination of controlled ring-opening polymerization (CROP) and coupling reaction. First, eight-arm star-shaped poly(E-caprolactone)s (SPCL) with a resorcinarene core were synthesized using octamethyl tetraundecylresorcinarene octaacetate as octa-initiator and yttrium tris(2,6-di-tert-butyl-4-methylphenolate)[Y(DBMP)3] as catalyst. Then the coupling reaction was carried out between SPCL and carboxyl-terminated methoxy poly(ethylene glycol)s (mPEG-COOH) in the presence of N,N’-dicyclohexylcarbodiimide (DCC) and4-dimethylaminopyridine (DMAP), resulting in eight-arm star-shaped SPCL-b-PEG with controlled molecular weight and well-defined architecture. Furthermore, these amphiphilic eight-arm SPCL-b-PEG could self-assemble into micelles with low critical micellar concentrations (CMC), which was characterized by fluorescent spectroscopy. Moreover, indomethacin loaded micelles with high drug loading content and high encapsulation efficiency were prepared, which is probably due to the highly branched architecture and the host-guest interaction between indomethacin and resorcinarene core moieties. The morphologies of micelles were characterized by transmission electron microscopy (TEM), which exhibit diverse nanostructures varied by the drug loading contents. In vitro drug release of indomethacin from SPCL-b-PEG micelles was carried out in PBS, from which a sustained release behavior was observed. SPCL-b-PEG copolymer micelles have no cytotoxicity, making it a potential as drug delivery carriers.