Glycinated Fullerenes for Tamoxifen Intracellular Delivery With Improved Anticancer Activity and Pharmacokinetics

Abstract

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.

Keywords:

• bioavailability
• biocompatible
• chemotherapy
• drug delivery
• hemolysis
• linker
• MCF-7
• N-desmethyl tamoxifen
• protein binding

Acknowledgements

D Chitkara from Birla Institute of Technology & Science, Pilani, India is warmly acknowledged for the kind support offered for the micromeritic studies. University Grant Commission, New Delhi, India is highly acknowledged for Rajeev Gandhi National Fellowship to M Kumar (F1–17.1/2014–15/RGNF-2014–15 ST-RAJ-73879/(SA-III/Website).

Financial & competing interests disclosure

The University Grant Commission, New Delhi, India and the Department of Science and Technology are acknowledged for the financial support in the form of UGC-Start-Up Grant (F.30–18/2014BSR). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.