Green Synthesis of Niosomal Dual Drug Delivery Systems for Synergistic Anticancer Therapy

Abstract

Conventional chemotherapy exhibits limited therapeutic efficacy against multidrug-resistant cancers due to systemic toxicity and drug resistance mechanisms. In response to this challenge, this work puts forward a nano-strategy based on binary tumor-killing action to improve the therapeutic efficacy mainly introducing the synthesis of niosomes formulations with two anticancer agents per carrier using the environmentally friendly probe sonication method. Surfactants used in the niosomes were poloxamer and sorbitan monostearate, while the hydrophilic and hydrophobic anticancer drugs of optimal characteristic properties selected, were Doxorubicin and Methotrexate, respectively. Characterizations of the new compounds included elemental analysis, absorption spectra, percentage composition, biocompatible resonance, infrared, and UV-Vis analysis, where changes in the pattern of absorption were used to determine the cytotoxicity against MCF-7 cancer cells and HEK 293 normal cells. The formed niosomes were small and of good size range of 137 nm to 893 nm and had high entrapment efficiencies of between 91.564% and 94.99%. The durability tests in four weeks showed that stability has not affected the particle size; thus, the structures are cohesive. It was observed that niosome formulations provided smooth and controlled patterns of drug release and that doxorubicin extended its release considerably while the dissolution rate of Methotrexate was boosted significantly. This controlled release positively impacted the cellular uptake and the drug circulation time inside the tumor mass, thus increasing the cytotoxicity effect of both drugs on MCF-7 cells. Both drugs in the niosomes also show a synergistic effect, which overcomes the multidrug resistance mechanism. In addition, the encapsulation strategy lowered cytotoxicity in normal HEK 293 cells, showing selective toxicity and the formulations' safety. In conclusion, the niosomes formulations containing doxorubicin and Methotrexate produced stable and small-sized vesicles with better release profiles, higher cellular uptake, low toxicity, and maximum tumor growth inhibition. These results suggest that dual drug- xv loaded niosomes are a more effective and safe therapeutic approach than conventional chemotherapy to treat multidrug-resistant cancers.