Charu Misra1, Manish Kumar1, Gajanand Sharma2, Rajendra Kumar3, Bhupinder Singh2,3, Om Prakash Katare3, Kaisar Raza1. 1. Department of Pharmacy, School of Chemical Sciences & Pharmacy, Central University of Rajasthan, Bandar Sindri, Ajmer, Rajasthan 305817, India. 2. University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies, Panjab University, Chandigarh 160014, India. 3. UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites, Panjab University, Chandigarh 160014, India.
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.
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.
Entities:
Keywords:
MCF-7; N-desmethyl tamoxifen; bioavailability; biocompatible; chemotherapy; drug delivery; hemolysis; linker; protein binding
Authors: Konstantin N Semenov; Daria A Ivanova; Sergei V Ageev; Andrey V Petrov; Nikita E Podolsky; Ekaterina M Volochaeva; Ekaterina M Fedorova; Anatolii A Meshcheriakov; Egor E Zakharov; Igor V Murin; Vladimir V Sharoyko Journal: Sci Rep Date: 2021-04-16 Impact factor: 4.379
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