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Mol Pharm. 2016 Jul 5;13(7):2423-32. doi: 10.1021/acs.molpharmaceut.6b00183. Epub 2016 May 27.

Conjugation of Docetaxel with Multiwalled Carbon Nanotubes and Codelivery with Piperine: Implications on Pharmacokinetic Profile and Anticancer Activity.

Author information

1
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan , Bandar Sindri, Distt. Ajmer, Rajasthan 305817, India.
2
Division of Cancer Pharmacology, Indian Institute of Integrative Medicine , Jammu 180001, India.
3
Department of Biotechnology, Banasthali Vidhyapith University , P.O. Banasthali Vidhyapith, Vanasthali, Rajasthan 304022, India.
4
Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh 160014, India.

Abstract

Nanotechnology-based drug products are emerging as promising agents to enhance the safety and efficacy of established chemotherapeutic molecules. Carbon nanotubes (CNTs), especially multiwalled CNTs (MWCNTs), have been explored for this potential owing to their safety and other desired attributes. Docetaxel (DTX) is an indispensable anticancer agent, which has wide applicability in variety of cancers. However, the potential of DTX is still not completely harvested due to problems like poor aqueous solubility, low tissue permeability, poor bioavailability, high first pass metabolism, and dose-related toxicity. Hence, it was proposed to attach DTX to MWCNTs and coadminister it along with piperine with an aim to enhance the tissue permeation, anticancer activity, and bioavailability. The Fourier transform infrared, UV, and NMR spectroscopic data confirmed successful conjugation of DTX to MWCNTs and adsorption of piperine onto MWCNTs. The codelivery MWCNT-based system offered drug release moderation and better cancer cell toxicity than that of plain DTX as well as DTX-CNT conjugate. The pharmacokinetic profile of DTX was exceptionally improved by the conjugation, in general, and coadministration with piperine, in specific vis-à-vis plain drug. Hence, the dual approach of MWCNTs conjugation and piperine coadministration can serve as a beneficial option for enhancement of the performance of DTX in cancer chemotherapy.

KEYWORDS:

CYP3A4 inhibition; IV push; MCF-7; MDA-MB-231; adsorption; bioavailability; drug delivery; drug release; nanomedicine

[Indexed for MEDLINE]

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