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ABSTRACT Well-defined amphiphilic A8B4 miktoarm star copolymers with eight poly(ethylene glycol) chains and four poly(ε-caprolactone) arms (R-8PEG-4PCL) were prepared using 'click' reaction strategy and controlled ring-opening polymerization (CROP). First, multi-functional precursor (R-8N3-4OH) with eight azides and four hydroxyls was synthesized based on the derivatization of resorcinarene. Then eight-PEG-arm star polymer (R-8PEG-4OH) was prepared through 'click' reaction of R-8N3-4OH with pre-synthesized alkyne-terminated monomethyl PEG (mPEG-A) in the presence of CuBr/ N, N, N′, N″, N″′- pentamethyldiethylenetriamine (PMDETA) in DMF. Finally, R-8PEG-4OH was used as tetrafunctional macroinitiator to prepare resorcinarene-centered A8B4 miktoarm star copolymers via CROP of ε-caprolactone utilizing Sn(Oct)2 as catalyst at 100 °C. These miktoarm star copolymers could self-assemble into spherical micelles in aqueous solution with resorcinarene moieties on the hydrophobic/hydrophilic interface, and the particle sizes could be controlled by the ratio of PCL to PEG. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2824-2833. [ABSTRACT FROM AUTHOR]

Two calixarene derivatives (2a, 2b) have been synthesized and used as macro-initiators to prepare star-shaped poly( ε-caprolactone)s (SPCLs) via controlled ringopening polymerization of ε-caprolactone in the presence of yttrium tris(2,6-di- tert-butyl-4-methylphenolate) [Y(DBMP)3]. The molecular weight of SPCLs was characterized by end group 1H-NMR analyses and size-exclusion chromatography (SEC). The results indicate that SPCLs based on a calix[4]arene derivative (2a) are well-defined four-arm star polymers with reasonably narrow molecular weight distributions in the given molecular weight range, while SPCLs based on a calix[6]arene derivative (2b) are star polymers with not so defined structures. Differential scanning calorimetry (DSC) analyses suggest that the maximal melting point, the crystallization temperature and the degree of crystallinity of SPCLs increases with the increasing molecular weight and are lower than those of the liner poly( ε-caprolactone) (LPCL) counterpart. Furthermore, polarized optical microscopy (POM) indicates that SPCL exhibits irregular spherulites with poor morphology and slower crystallization rate, whereas LPCL shows fast crystallization rate and good spherulitic morphology. [ABSTRACT FROM AUTHOR]

The clinical utility of doxorubicin (DOX) is restricted by its severe side effects. Continuous efforts are aimed at developing efficacious DOX-delivery systems that may overcome the drawbacks of existing ones. Herein, we report a self-assembling prodrug forming high drug loading nanoparticles for DOX delivery. A low molecular weight polyethylene glycol (PEG) chain as the hydrophilic part was anchored to hydrophobic DOX via an acid-cleavable hydrazone bond to form the amphiphilic prodrug PEG-DOX. In aqueous solution, PEG-DOX formed nanoparticles with a diameter of ∼125 nm and extremely high drug loading (∼46 wt%). These nanoparticles were stable in PBS but released DOX in an acidic pH-triggered manner. Interestingly, taken up by cells via endocytosis, PEG-DOX bypassed the P-glycoprotein (P-gp)-mediated efflux of DOX, leading to drug accumulation in DOX-resistant human breast cancer cells (MCF-7/ADR). More importantly, PEG-DOX exhibited potent antitumor activity in vitro and in vivo, and showed significantly increased in vivo safety than free DOX. These encouraging data merit further preclinical and clinical development on PEG-DOX.