De novo synthesis of a MIL-125(Ti) carrier for thermal- and pH-responsive drug release.

Abstract

Microporous round cake-like (diameter: 900±100nm) MIL-125(Ti) carrier with a central metal (Ti) exhibiting bio-affinity and possessing a great potential to be used as drug release platform, has been synthesized in the present study. The thermal and pH responsiveness of drug delivery systems (DDS) are the most important parameters for drug release and can be provided through polymer coating techniques. The Pluronic F127 (F127) and chitosan (CH) monomers were inserted into the crystal lattice of MIL-125(Ti) carrier during the de novo synthesis process, which were subsequently loaded with doxorubicin (DOX). The results reveal particle size changes (ranged between 30 and 50%) from the original size of the MIL-125(Ti) carrier in response to temperature and pH when the carrier reaches acid environment. The drug release profiles have been completed through self-design device, which provides for the real-time release in the DOX amounts via UV-Vis spectra. The kinetics analysis was used to evaluate the R2 values of first order, Higuchi, Korsmeyer-peppas, and Weibull fitting equations, where the Weibull fitting indicated the best R2. An increase by 59.3% of DOX released under the acid status (pH=5.4) was observed, indicating that the CH-MIL-125(Ti) carrier is temperature and pH responsive. Moreover, the lattice explosion resulting from the temperature increase in the range of 25-42°C caused an increase in F127-MIL-125(Ti) by 30.8-38.3%. The simulated SAXS/WAXS studies for the microstructures of MIL-125(Ti) based DDS at different temperatures after polymer coating (F127-MIL-125(Ti)) provide the possible mechanism of lattice explosion. As such, the responsive Ti-MOF has a highly potential for use in the applications of cancer treatment.