Increased Drug-Loading Enhances the Activity of Ellipticine in Poly(N-(2-hydroxypropyl) Methacrylamide) PHPMA-Based Polymeric Micelles in 2D and 3D Cancer Cell Models

Polymeric micelles are widely used as multifunctional drug carriers of poorly water-soluble drugs, but the role of drug loading content is often overlooked. The purpose of this study is to investigate the cellular uptake and penetration of polymeric micelles with different drug loading contents and their effects on biological activities. In this study, poly(N-(2-hydroxypropyl) methacrylamide-co-methacrylic acid)-block-poly methyl methacrylate P(HPMA-co-MAA)-b-PMMA micelles are used as a nanocarrier for the encapsulation of the potent anticancer agent ellipticine (EPT). The micelles are loaded with various amounts of EPT and the physicochemical characteristics such as particle size, morphology, and zeta potential of blank and EPT loaded nanoparticles are studied. Moreover, fluorescent lifetime studies confirm that hydrophobic EPT is indeed in the PMMA micelle core. In vitro cytotoxicity tests using the glioma cell line U87MG reveal lower IC50 values when the cells are incubated with micelle with high drug loading content. The higher toxicity in micelles with higher drug loading content is associated with higher cellular uptake, which is monitored using laser scanning confocal microscopy and flow cytometry. Moreover, higher activity of micelles with higher drug loading is also observed in U87MG multicellular tumor spheroids although the difference is not significant.

Automated summary

Polymeric micelles with different drug loading contents were studied to investigate their cellular uptake, penetration, and effects on biological activities. The results showed that micelles with high drug loading content exhibited higher cellular uptake and toxicity.