Thermosensitive hydrogel for in situ-controlled methotrexate delivery

Methotrexate (MTX) is widely used for the treatment of various types of cancer; however, it has drawbacks such as low solubility, lack of selectivity, premature degradation, and side effects. To solve these weaknesses, a hydrogel with the ability to contain and release MTX under physiological conditions without burst release was synthesized. The hydrogel was fabricated with a poly(ɛ-caprolactone)-b-poly(ethylene glycol)-b-poly(ɛ-caprolactone) (PCL–PEG–PCL) triblock copolymer, synthesized by ring-opening polymerization. The characterizations by proton nuclear magnetic resonance spectroscopy and Fourier-transform infrared spectrometry confirmed the copolymer assembly, whereas the molecular weight analysis validated the PCL2000–PEG1000–PCL2000 structure. The copolymer aqueous solution exhibited sol–gel phase transition at 37°C and injection capacity. The hydrogel supported a load of 1,000 μg MTX·mL−1, showing a gradual and sustained release profile of the drug for 14 days, with a delivery up to 92% at pH 6.7. The cytotoxicity of the MTX-loaded hydrogel was performed by the methyl thiazole tetrazolium assay, showing a mean inhibitory concentration of 50% of MCF-7 cells (IC50) at 43 µg MTX·mL−1.

Supramolecularly cross-linked amphiphilic block copolymer assembly by the dipolar interaction of a merocyanine dye

Dipolar interaction driven dimerization of a merocyanine (MC) dye has been exploited to achieve non-covalently crosslinked stable micelles in water and reverse micelles in toluene with emissive properties from a MC-pendant amphiphilic block copolymer.

Generalizing the effects of chirality on block copolymer assembly

We explore the generality of the influence of segment chirality on the self-assembled structure of achiral–chiral diblock copolymers. Poly(cyclohexylglycolide) (PCG)-based chiral block copolymers (BCPs*), poly(benzyl methacrylate)-b-poly(d-cyclohexylglycolide) (PBnMA-PDCG) and PBnMA-b-poly(l-cyclohexyl glycolide) (PBnMA-PLCG), were synthesized for purposes of systematic comparison with polylactide (PLA)-based BCPs*, previously shown to exhibit chirality transfer from monomeric unit to the multichain domain morphology. Opposite-handed PCG helical chains in the enantiomeric BCPs* were identified by the vibrational circular dichroism (VCD) studies revealing transfer from chiral monomers to chiral intrachain conformation. We report further VCD evidence of chiral interchain interactions, consistent with some amounts of handed skew configurations of PCG segments in a melt state packing. Finally, we show by electron tomography [3D transmission electron microscope tomography (3D TEM)] that chirality at the monomeric and intrachain level ultimately manifests in the symmetry of microphase-separated, multichain morphologies: a helical phase (H*) of hexagonally, ordered, helically shaped tubular domains whose handedness agrees with the respective monomeric chirality. Critically, unlike previous PLA-based BCP*s, the lack of a competing crystalline state of the chiral PCGs allowed determination that H* is an equilibrium phase of chiral PBnMA-PCG. We compared different measures of chirality at the monomer scale for PLA and PCG, and argued, on the basis of comparison with mean-field theory results for chiral diblock copolymer melts, that the enhanced thermodynamic stability of the mesochiral H* morphology may be attributed to the relatively stronger chiral intersegment forces, ultimately tracing from the effects of a bulkier chiral side group on its main chain.