Glycinated fullerenes for tamoxifen intracellular delivery with improved anticancer activity and pharmacokinetics

Aim: Glycine-tethered C60-fullerenes were conjugated with N-desmethyl tamoxifen and evaluated for drug delivery benefits. Materials & methods: C60-fullerenes were functionalized with glycine, and N-desmethyl tamoxifen was conjugated, employing a linker and characterized for micromeritics, drug loading, drug release and evaluated for cancer cell toxicity, cellular uptake and pharmacokinetics. Results: The nanoconjugate with a drug entrapment efficiency of 82.71 ± 6.23% and a drug loading of 66.01 ± 4.98% was hemocompatibile with appreciable MCF-7 cytotoxicity. The confocal results confirmed enhanced uptake of conjugate. Interestingly, pharmacokinetic outcomes of the conjugate were superior and the area under the curve was enhanced by approximately three-times, whereas the drug clearance was reduced by around five-times, after single intravenous injection. Conclusion: The conjugation assured improved availability of drug in a biological system for prolonged duration as well as in the interiors of target cells with a promise of enhanced efficacy and compatibility.

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