Development of pH and thermo-responsive smart niosomal carriers for delivery of gemcitabine to the breast cancer cells

Abstract

The utilization of intelligent drug carriers in cancer therapy has emerged as a transformative paradigm in modern oncology. These advanced drug delivery systems exploit the distinctive characteristics of cancer cells and their surrounding microenvironment to attain precise and targeted drug release at the tumor site. In this study, we aim to introduce a novel niosome formulation endowed with dual-responsive properties, pH, and thermo-sensitivity, to enhance drug release precisely within the intended target site. Therefore, thin-film method was used for the fabrication of niosomes, incorporating dipalmitoylphosphatidylcholine (DPPC), as thermoresponsive phospholipid, and citraconic anhydride, as pH-responsive linker. The fabricated niosomes were evaluated through physicochemical analysis using Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and scanning electron microscopy (SEM). Additionally, the entrapment efficiency (EE%) and drug release pattern of gemcitabine (GEM) were quantified at different conditions using UV-Visible spectroscopy. The bioactivity of these niosomes was also evaluated via cytotoxicity assay and flow cytometry. Results of physicochemical analysis verified the successful fabrication of spherical nanoparticles, with a size range of about 100-150 nm and a neutral surface charge. Furthermore, the fabricated niosomes showed sensitivity to acidic pH (6.5) and temperature exceeding the transition temperature (Tc) of the DPPC (41.5 degrees C). Importantly, the drug release profile indicated about 10-17% enhancement in drug release for the dual-stimuli platform in comparison to the single-stimuli ones. The cytotoxicity assay and flow cytometry analysis demonstrated an approximate 10% increase in cytotoxicity and about a 2.5-fold rise in apoptosis induction for the dual-stimuli responsive platform in contrast to the free drug. In conclusion, this dual-stimuli responsive nanocarrier presents a promising strategy to enhance the specificity and efficacy of cancer chemotherapy while simultaneously reducing the adverse side effects experienced by patients.