title: Diaminosulfide based polymer microparticles as cancer vaccine delivery systems.
abstract: The aim of the research presented here was to determine the characteristics and immunostimulatory capacity, in vivo, of antigen and adjuvant co-loaded into microparticles made from a novel diaminosulfide polymer, poly(4,4'-trimethylenedipiperdyl sulfide) (PNSN), and to assess their potential as cancer vaccine vectors. PNSN microparticles co-loaded with the antigen, ovalbumin (OVA), and adjuvant, CpG 1826, (PNSN(OVA + CpG)) were fabricated and characterized for size (1.64 μm diameter; PDI=0.62), charge (-23.1 ± 0.3), and loading efficiencies of antigen (7.32 μg/mg particles) and adjuvant (0.95 μg/mg particles). The ability of PNSN(OVA + CpG) to stimulate cellular and humoral immune responses in vivo was compared with other PNSN microparticle formulations as well as with poly(lactic-co-glycolic acid)(PLGA)-based microparticles, co-loaded with OVA and CpG (PLGA(OVA + CpG)), an adenovirus encoding OVA (Ad5-OVA), and OVA delivered with incomplete Freund's adjuvant (IFA(OVA)). In vivo OVA-specific IgG1 responses, after subcutaneous prime/boosts in mice, were similar when PNSN(OVA + CpG) and PLGA(OVA + CpG) were compared and the presence of CpG 1826 within the PNSN microparticles demonstrated significantly improved responses when compared to PNSN microparticles loaded with OVA alone (PNSN(OVA)), plus or minus soluble CpG 1826. Cellular immune responses to all particle-based vaccine formulations ranged from being negligible to modest with PNSN(OVA + CpG) generating the greatest responses, displaying significantly increased levels of OVA-specific CD8+ T lymphocytes compared to controls and IFA(OVA) treated mice. Finally, it was shown that of all vaccination formulations tested PNSN(OVA + CpG) was the most protective against subsequent challenge with an OVA-expressing tumor cell line, E.G7. Thus, microparticles made from poly(diaminosulfide)-based macromolecules possess promising potential as vaccine vectors and, as demonstrated here, may have impact as cancer vaccines in particular.
authors.affiliation: Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Geary
authors.affiliation: Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, USA; Guangdong Pharmaceutical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Qiaohong
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, USA.
authors.forename: Vijaya B
authors.initials: VB
authors.lastname: Joshi
authors.affiliation: Department of Chemistry, College of Liberal Arts and Sciences, University of Iowa, Iowa City, USA.
authors.forename: Ned B
authors.initials: NB
authors.lastname: Bowden
authors.affiliation: Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, USA. Electronic address: aliasger-salem@uiowa.edu.
authors.forename: Aliasger K
authors.initials: AK
authors.lastname: Salem
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D013440:Sulfides / Q000737:chemistry*; D013945:Thymoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013953:Thymus Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; C423449:CpG ODN 1826; D004337:Drug Carriers; D009838:Oligodeoxyribonucleotides; D011108:Polymers; D013440:Sulfides; C000611298:poly(4,4'-trimethylenedipiperdyl sulfide); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin; D005620:Freund's Adjuvant
keywords: Cancer vaccine; CpG, PLGA; Microparticles; Nanoparticles, biodegradable polymer, antigen; PNSN; Poly(4,4′-trimethylenedipiperdyl sulfide)