Journal article
Diaminosulfide based polymer microparticles as cancer vaccine delivery systems
Journal of controlled release, Vol.220(Pt B), pp.682-690
12/28/2015
DOI: 10.1016/j.jconrel.2015.09.002
PMCID: PMC4688223
PMID: 26359124
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 (1.64μm diameter; PDI=0.62), charge (−23.1±0.3), and loading efficiencies of antigen (7.32μg/mg particles) and adjuvant (0.95μg/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. [Display omitted]
Details
- Title: Subtitle
- Diaminosulfide based polymer microparticles as cancer vaccine delivery systems
- Creators
- Sean M Geary - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, USAQiaohong Hu - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, USAVijaya B Joshi - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, USANed B Bowden - Department of Chemistry, College of Liberal Arts and Sciences, University of Iowa, Iowa City, USAAliasger K Salem - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, USA
- Resource Type
- Journal article
- Publication Details
- Journal of controlled release, Vol.220(Pt B), pp.682-690
- DOI
- 10.1016/j.jconrel.2015.09.002
- PMID
- 26359124
- PMCID
- PMC4688223
- NLM abbreviation
- J Control Release
- ISSN
- 0168-3659
- eISSN
- 1873-4995
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 12/28/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Chemistry; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9983985833002771
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