Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 473, Issue 1-2, Pages 296-303Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2014.06.052
Keywords
Oral delivery; Vaccine; Polymeric lipid nanoparticles; M-cell targeting; Toll-like receptor agonist
Categories
Funding
- 973 Program [2013CB531500]
- 863 Program [2012AA02A406]
- Knowledge Innovation Program of the Chinese Academy of Sciences [KSCX2-EW-R-19]
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Oral delivery of antigens is patient-friendly and efficient way of treating intestinal infections. However, the efficacy of oral vaccines is limited by degradation in the gastrointestinal (GI) tract and poor absorption by enterocytes and antigen-presenting cells (APC). Here we report ulex europaeus agglutinin-1 (UEA-1) conjugated poly (D,L-lactide-co-glycolide) (PLGA)-lipid nanoparticles (NP) containing a Toll-like receptor (TLR)-agonist monophosphoryl lipid A (MPL) as an oral vaccine delivery system. The uniform-sized PLGA-lipid NPs (simplified as lipid NPs) were produced by the premix membrane emulsification method. They can protect the entrapped model antigen ovalbumin (OVA) from exposure to the GI tract and release the OVA in a controlled manner. With UEA-1 and MPL modification, the UEA-MPL/lipid NPs can be effectively transported by M-cells and captured by mucosal dendritic cells (DCs). After in vivo vaccination, the OVA-UEA-MPL/lipid NPs stimulated the most effective mucosal IgA and serum IgG antibodies during the oral formulations. These results suggest that this MPL containing M-cell targeted lipid NP can potentially be used as a universally robust oral vaccine delivery system. (C) 2014 Elsevier B.V. All rights reserved.
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