Surface modification of tungsten disulfide nanosheets with pH/Thermosensitive polymer and polyethylenimine dendrimer for near-infrared triggered drug delivery of letrozole

Abstract

In the present work, pH and thermosensitive polymer, N-isopropylacrylamide-co-allyl acetoacetate modified polyethylenimine dendrimer-grafted tungsten disulfide, is successfully synthesized for triggered letrozole delivery for cancer chemotherapy. The nanocarrier was characterized by Fourier-transform infrared spectra, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, elemental analysis, and X-ray diffraction techniques. Different parameters influencing the sorption of drug such as pH, contact time, and temperature were studied to optimize the operating conditions. It was shown that drug release is enhanced under the near infrared laser irradiation, indicating that the nanocarrier can be used as dual responsive systems, with drug release controllable through laser irradiation. Moreover, after 6 h of simulated release in vitro, the letrozole release amount of the nanocarrier was 88.76 % at pH 5.6 (37 °C), 99.47 % at pH 5.6 (45 °C), 33.60 % at pH 7.4 (37 °C), and 73.35 % at pH 7.4 (45 °C), showing the pH and thermo-responsiveness. The different release kinetic models were investigated and it has been shown that release curve of drug best followed the Higuchi model for the release of letrozole from the nanocarrier. The release of letrozole from the nanocarrier occurred through non-Fickian diffusion mechanism. Upon 808 nm near laser irradiation, it shown that 100 % of letrozol was released. The pH and thermosensitive polymer absorb the NIR light and as a result begin to dissipate heat. This heat produced induces a shrinkage of the polymer facilitating the release of the drug. Also, adsorption of drug on the pH and thermosensitive polymer is best explained by Langmuir isotherm and pseudo-second-order kinetic models.