Journal
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 106, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.msec.2019.110294
Keywords
Controlled DNA delivery; Nanoparticle-in-microsphere (NIM) hybrid system; DNA vaccine; S/O/W emulsion; Prime-boost
Categories
Funding
- National Natural Science Foundation of China [51773107, 51690152, 21704051]
- Taishan Scholars Program [tsqn201812072]
- Shandong Provincial Natural Science Foundation, China [ZR2017ZB0105]
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Controlled release strategies of DNA vaccine hold promise for the design of in vivo vaccination platforms, yet the formulation and sustained delivery still pose a substantial challenge. In this study, we developed a novel hybrid dual-particulate delivery system, nanoparticle-in-microsphere (NIM), to integrate the advantages of nano-sized polymer/DNA polyplex with the sustained-release microsphere for DNA vaccine delivery. The nano-sized cores, consisting of polyethylene glycol-graft-polyethylenimine (PEG-g-PEI)/DNA polyplexes, were formulated into PLGA microspheres using a solid-in-oil-in-water (S/O/W) emulsion. The PEG block was used as stabilizing excipient to make DNA soluble and stable in organic solvent to prevent the inactivation of DNA at aqueous-organic interface during encapsulation. The fashion of DNA in dry solid state greatly increased the encapsulation efficiency of DNA in NIMs. This new formulation exhibited a burst release less than 15% and then sustain release close to zero-order kinetics in physiological environment In addition, the microspheres showed pH-sensitivity and degraded faster in lysosomal compartments, which contributed to the accelerated intracellular release kinetics of DNA. Finally, intramuscular injection of NIMs encoding HIV proteins elicited distinct humoral and cellular immune response in mice at low dose. These results thus may aid NIM-based vaccination towards more extensive clinical evaluations.
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