Tailoring micellar nanocarriers for pemetrexed in breast cancer: design, fabrication and <i>in vitro</i> evaluation

<b>Aim:</b> To investigate the pemetrexed encapsulated polymeric mixed micelles (PMMs) against breast cancer treatment. <b>Methods:</b> We meticulously optimized the formulation and conducted extensive characterizations, including photon correlation spectroscopy for micellization, advanced analytical techniques and <i>in vitro</i> cell line assessments. <b>Results:</b> The PMM exhibited favorable characteristics, with a spherical morphology, hydrodynamic particle size of 19.58 ± 0.89 nm, polydispersity index of 0.245 ± 0.1, and a surface charge of -9.70 ± 0.61 mV. Encapsulation efficiency and drug payload reached 96.16 ± 0.37% and 4.5 ± 0.32%, respectively. Cytotoxicity analysis indicated superior efficacy of the PMM over the drug solution. <b>Conclusion:</b> The PMM formulation exhibited controlled release of the drug, and demonstrated enhanced cytotoxicity against breast cancer cells, highlighting its therapeutic promise. Breast cancer is a profoundly complex malignancy characterized by extensive genetic and clinical diversity, displaying a wide array of clinicopathological and morphological attributes and demonstrating variable responses to various therapeutic modalities. In this investigation, we delved into the intricate realm of medical science by examining the ternary amalgamation of Pluronic F127, Pluronic F68 and D-α-tocopheryl PEG 1000 succinate to encapsulate pemetrexed within a composite of polymeric mixed micelles. Pemetrexed, a pharmacological agent, operates as an antimetabolite, effectively inhibiting critical enzymes such as thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, which play pivotal roles in DNA synthesis. The meticulously prepared formulation underwent a process of optimization, followed by exhaustive characterization studies. The micellization phenomena were subjected to meticulous scrutiny using photon correlation spectroscopy. We employed advanced analytical techniques including Fourier transform infrared spectroscopy, differential scanning calorimetry, powder x-ray diffraction, 1D proton nuclear magnetic resonance (NMR) spectroscopy, one-dimensional selective rotating-frame Overhauser effect NMR spectroscopy and 2D proton–proton rotating-frame Overhauser effect NMR spectroscopy to elucidate the intricate interplay between the formulation's excipients and the therapeutic agent. We conducted rigorous assessments of drug and formulation dissolution behavior, along with <i>in vitro</i> studies on MCF-7 cell lines, to ascertain the formulation's efficacy against breast cancer. Our <i>in vitro</i> drug-release investigation unveiled a sustained release profile, outperforming the drug solution, with release kinetics adhering to the Higuchi model. NMR spectroscopy confirmed the presence of noncovalent interactions between the drug and the polymer components of the formulation. Our comprehensive cytotoxicity analysis demonstrated that the meticulously developed formulation exhibits superior efficacy compared with the unadulterated drug solution. The culmination of these findings unequivocally suggests that the polymeric mixed micelles represent a promising paradigm in the realm of drug-delivery systems, holding great potential for the treatment of breast cancer.