Enhanced methotrexate delivery and efficacy with probe‐sonicated chitosan nanoparticles

Small particle size is an important parameter for minimized aggregation, improved cellular uptake and biocompatibility. Nanoparticle size can be controlled by the method used during synthesis. Cationic chitosan nanoparticles (CNPs) are advantageous for endosomal escape; however, obtaining micrometer‐sized nanoparticles and formation of aggregates during the gelation process reduce cellular uptake. Probe sonication is a technique used to reduce the nanoparticle size, which is determined by various factors, the most important one being the amplitude. In this study, two amplitudes were used to synthesize and characterize CNPs in terms of their size, release, toxicity and cellular internalization successes. The one with superior characteristics was chosen to produce CNPs to be loaded with methotrexate (MTX), an anticancer agent. The endosomal escape and effectiveness of CNPs was tested in cervical cancer cells (HeLa). The size of nanoparticles was below 200 nm. The release was slower, and cellular internalization was higher in CNPs synthesized with lower amplitude. The encapsulation efficiency was 82% and MTX was released for 5 days. CNPs significantly increased the efficacy of MTX which was attributed to efficient internalization and successful endosomal escape. These findings reveal that synthesized MTX‐loaded CNPs may be used as an alternative treatment strategy for cervical cancer with possible lower side effects.