The effect of architecture/composition on the pH sensitive micelle properties and in vivo study of curcuminin-loaded micelles containing sulfobetaines

Abstract

The polymeric architecture greatly influences the properties of polymer drug carriers. In this study, copolymers of poly(ε-caprolactone)-b-poly(N,N-diethylaminoethyl methacrylate)-r-poly(N-(3-sulfopropyl)-N-methacryloxyethy-N,N-diethylammoniumbetaine) with linear (L-PCL-PDEASB) and four-armed star-shape (4s-PCL-PDEASB) were designed and prepared to explore the relationship between the architecture/composition and the micelle properties. The structures of these copolymers were characterized by nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), elemental analysis, gel permeation chromatograph (GPC), differential scanning calorimetry (DSC), and water contact angle (WCA) measurements. The results showed that the copolymer composition/structure affects the thermal properties, hydrophilicity, micelle properties, pH sensitivity and drug releasing performance. In cytotoxicity experiment the micelles of star-shaped copolymer displayed lower cell toxicity than those of the linear copolymer with the same composition. The drug release rate of the curcumin-loaded micelles was related to the sulfobetaine units and was very different for different copolymer micelles. The curcumin-loaded micelles of star-shaped copolymer prolonged the retention time of curcumin in blood circulation in pharmacokinetic experiments and accumulated more in tumor sites than the free curcumin in breast carcinoma bearing mice in drug distribution experiments. The tissue section images illustrated that the curcumin-loaded micelles could reduce curcumin damage to the liver and lungs. Therefore, the pH sensitive micelles of star-shaped copolymer containing sulfobetaines with suitable composition are promising carriers.