title: Disintegration and cancer immunotherapy efficacy of a squalane-in-water delivery system emulsified by bioresorbable poly(ethylene glycol)-block-polylactide.
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.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, 11466 Taipei, Taiwan; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35053 Miaoli, Taiwan.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Chen
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35053 Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, 40402 Taichung, Taiwan.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35053 Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, 40402 Taichung, Taiwan.
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Leng
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35053 Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, 40402 Taichung, Taiwan.
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Chen
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35053 Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, 40402 Taichung, Taiwan.
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, 11466 Taipei, Taiwan; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35053 Miaoli, Taiwan. Electronic address: huangminghsi@nhri.org.tw.
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Huang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D004655:Emulsions; D006868:Hydrolysis; D007167:Immunotherapy; D007773:Lactates / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013185:Squalene / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000276:immunology; D014867:Water / Q000008:administration & dosage
chemical_list: D001672:Biocompatible Materials; D004655:Emulsions; D007773:Lactates; C088513:poly(lactic acid-ethylene glycol); D014867:Water; D011092:Polyethylene Glycols; D013185:Squalene
keywords: Bioresorbable polymer; Cancer immunotherapy; Emulsion disintegration; Tumor-associated antigen; Vaccine adjuvant