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Folate-Functionalized Thiomeric Nanoparticles for Enhanced Docetaxel Cytotoxicity and Improved Oral Bioavailability

Abstract

To achieve remotely directed delivery of anticancer drugs, surface-decorated nanoparticles with ligands are reported. In this study, folic acid– and thiol-decorated chitosan nanoparticles loaded with docetaxel (DTX-NPs) were prepared for enhanced cellular internalization in cancer cells and improved oral absorption. The DTX-NPs were explored through in vitro and in vivo parameters for various parameters. The DTX-NPs were found to be monodisperse nanoparticles with an average particle size of 158.50 ± 0.36 nm, a polydispersity index of 0.36 ± 0.0, a zeta potential of + 18.30 ± 2.52 mV, and an encapsulation efficiency of 71.47 ± 5.62%. The drug release from DTX-NPs followed the Korsmeyer-Peppas model with about 78% of drug release in 12 h. In in vitro cytotoxicity studies against folate receptor, positive MDA-MBB-231 cancerous cells showed improved cytotoxicity with IC50 of 0.58 μg/mL, which is significantly lower as compared to docetaxel (DTX). Ex vivo permeation enhancement showed an efflux ratio of 0.99 indicating successful transport across the intestine. Oral bioavailability was significantly improved as Cmax and AUC were higher than DTX suspension. Overall, the results suggest that DTX-NPs can be explored as a promising carrier for oral drug delivery.

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Correspondence to Muhammad Farhan Sohail.

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Sajjad, M., Khan, M.I., Naveed, S. et al. Folate-Functionalized Thiomeric Nanoparticles for Enhanced Docetaxel Cytotoxicity and Improved Oral Bioavailability. AAPS PharmSciTech 20, 81 (2019). https://doi.org/10.1208/s12249-019-1297-z

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KEY WORDS

  • docetaxel
  • nanoparticles
  • thiolated chitosan
  • folic acid
  • oral bioavailability