Paclitaxel-encapsulated core-shell nanoparticle of cetyl alcohol for active targeted delivery through oral route

Nanomedicine (Lond). 2019 Aug;14(16):2121-2150. doi: 10.2217/nnm-2018-0419. Epub 2019 Aug 14.

Abstract

Aim: Paclitaxel (PTX) has no clinically available oral formulations. Cetyl alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase that are overexpressed in cancer cells. So, PTX-encapsulated core-shell nanoparticle of cetyl alcohol (PaxSLN) could target the cancer cells through oral route. Materials & methods: PaxSLN was synthesized using microemulsion template. Efficiency of PaxSLN was evaluated by ALDEFLUOR™, multicellular tumor spheroid formation inhibition assays and CT26 colorectal carcinoma animal model. Pharmacokinetics and biodistribution studies were done in Sprague Dawley rats. Results: PTX was encapsulated at the core of approximately 78 nm PaxSLN. PaxSLN targeted aldehyde dehydrogenase overexpressing cells. Its oral bioavailability was approximately 95% and chemotherapeutic efficacy was better than Taxol® and nab-PTX. Conclusion: A novel oral nanoformulation of PTX was developed.

Keywords: ALDEFLUOR™ assay; alcohol dehydrogenase (ADH); aldehyde dehydrogenase (ALDH); cancer stem cell; cetyl alcohol nanoparticle; core–shell nanoparticle; nanoformulation; oral anticancer drug delivery; paclitaxel; solid lipid nanoparticle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Administration, Oral
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Colorectal Neoplasms / drug therapy
  • Fatty Alcohols / chemistry*
  • Flow Cytometry
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Paclitaxel / administration & dosage
  • Paclitaxel / chemistry*
  • Paclitaxel / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Spectroscopy, Fourier Transform Infrared
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Fatty Alcohols
  • cetyl alcohol
  • Paclitaxel