Disintegration and cancer immunotherapy efficacy of a squalane-in-water delivery system emulsified by bioresorbable poly(ethylene glycol)-block-polylactide

Biomaterials. 2014 Feb;35(5):1686-95. doi: 10.1016/j.biomaterials.2013.11.004. Epub 2013 Nov 20.

Abstract

Vaccine adjuvant is conferred on the substance that helps to enhance antigen-specific immune response. Here we investigated the disintegration characteristics and immunotherapy potency of an emulsified delivery system comprising bioresorbable polymer poly(ethylene glycol)-polylactide (PEG-PLA), phosphate buffer saline (PBS), and metabolizable oil squalane. PEG-PLA-stabilized oil-in-water emulsions show good stability at 4 °C and at room temperature. At 37 °C, squalane/PEG-PLA/PBS emulsion with oil/aqueous weight ratio of 7/3 (denominated PELA73) was stable for 6 weeks without phase separation. As PEG-PLA being degraded, 30% of free oil at the surface layer and 10% of water at the bottom disassociated from the PELA73 emulsion were found after 3 months. A MALDI-TOF MS study directly on the DIOS plate enables us to identify low molecular weight components released during degradation. Our results confirm the loss of PLA moiety of the emulsifier PEG-PLA directly affected the stability of PEG-PLA-stabilized emulsion, leading to emulsion disintegration and squalane/water phase separation. As adjuvant for cancer immunotherapeutic use, an HPV16 E7 peptide antigen formulated with PELA73 plus immunostimulatory CpG molecules could strongly enhance antigen-specific T-cell responses as well as anti-tumor ability with respected to non-formulated or Alum-formulated peptide. Accordingly, these advances may be a potential immunoregulatory strategy in manipulating the immune responses induced by tumor-associated antigens.

Keywords: Bioresorbable polymer; Cancer immunotherapy; Emulsion disintegration; Tumor-associated antigen; Vaccine adjuvant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials*
  • Emulsions
  • Hydrolysis
  • Immunotherapy*
  • Lactates / administration & dosage
  • Lactates / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / drug therapy*
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Squalene / administration & dosage*
  • T-Lymphocytes / immunology
  • Water / administration & dosage

Substances

  • Biocompatible Materials
  • Emulsions
  • Lactates
  • poly(lactic acid-ethylene glycol)
  • Water
  • Polyethylene Glycols
  • Squalene