Local delivery of cannabinoid-loaded microparticles inhibits tumor growth in a murine xenograft model of glioblastoma multiforme

PLoS One. 2013;8(1):e54795. doi: 10.1371/journal.pone.0054795. Epub 2013 Jan 22.

Abstract

Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Δ(9)-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) - the two major ingredients of marijuana - have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-ε-caprolactone microparticles as an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1:1 w:w) of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Cannabidiol / administration & dosage*
  • Cannabis / chemistry
  • Cell Proliferation / drug effects
  • Dronabinol / administration & dosage*
  • Drug Delivery Systems
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Humans
  • Mice
  • Polymers / administration & dosage
  • Transplantation, Heterologous

Substances

  • Polymers
  • Cannabidiol
  • Dronabinol

Grant support

This work was supported by grants from the Spanish Ministry of Science and Innovation (MICINN) (PS09/01401 to GV), Comunidad Autónoma de Madrid (PR1/06-14474-B to AITS) and Complutense University (CCG07-UCM/BIO-2824 to AITS). DH was recipient of a FPU fellowship from MICINN. ML was sequentially recipient of a “Juan de la Cierva” contract, a postdoctoral contract from Spanish Ministry of Education and Science and a postdoctoral contract from Comunidad de Madrid. ST was recipient of a research training contract from Comunidad de Madrid. GW Pharmaceuticals funded part of the research that was performed in GV's laboratory. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.