Twin-screw extruded lipid implants containing TRP2 peptide for tumour therapy

Eur J Pharm Biopharm. 2017 May:114:79-87. doi: 10.1016/j.ejpb.2016.12.033. Epub 2017 Jan 16.

Abstract

Much effort has been put in the development of specific anti-tumour immunotherapies over the last few years, and several studies report on the use of liposomal carriers for tumour-associated antigens. In this work, the use of lipid implants, prepared using two different extruders, was investigated for sustained delivery in tumour therapy. The implants consisted of cholesterol, soybean lecithin, Dynasan 114, trehalose, ovalbumin (OVA) or a TRP2 peptide, and Quil-A. Implants were first produced on a Haake Minilab extruder, and then a scale-down to minimal quantities of material on a small scale ZE mini extruder was performed. All formulations were characterised in terms of extrudability, implant properties and in vitro release behaviour of the model antigen ovalbumin. The type of extruder used to produce the implants had a major influence on implant properties and the release behaviour, demonstrating that extrusion parameters and lipid formulations have to be individually adapted to each extrusion device. Subsequently, lipid implants containing TRP-2 peptide were extruded on the ZE mini extruder and investigated in vitro and in vivo. The in vivo study showed that mice having received TRP2 loaded implants had delayed tumour growth for 3days compared to groups having received no TRP2.

Keywords: Lipid implants; Ovalbumin; Quil-A; Sustained release of antigen; TRP2; Twin-screw extrusion; Vaccine delivery.

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Animals
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / pharmacology*
  • Cell Line, Tumor
  • Delayed-Action Preparations
  • Drug Compounding
  • Drug Implants
  • Excipients
  • Immunotherapy / methods
  • Lipids / chemistry*
  • Male
  • Membrane Proteins / administration & dosage*
  • Membrane Proteins / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Neoplasms / prevention & control*
  • Neoplasms, Experimental / drug therapy
  • Ovalbumin / chemistry
  • Peptide Fragments / administration & dosage*
  • Peptide Fragments / pharmacology*
  • Quillaja Saponins / chemistry

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Delayed-Action Preparations
  • Drug Implants
  • Excipients
  • Lipids
  • Membrane Proteins
  • Peptide Fragments
  • Quillaja Saponins
  • peptide SVYDFFVWL
  • Quil A
  • Ovalbumin