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Incorporation of SDF‐1α into Pre‐formed Dextran Sulfate and Chitosan Nanoparticles
Author(s) -
Zaman Paula,
Wang Julia,
Li Tina,
Wang Weiping,
Kohane Daniel,
Loscalzo Joseph,
Zhang YingYi
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb645
Subject(s) - chemistry , zeta potential , dispersity , chitosan , dextran , in vivo , nanoparticle , biophysics , nuclear chemistry , biochemistry , nanotechnology , materials science , polymer chemistry , microbiology and biotechnology , biology
Dextran sulfate (DS) and chitosan (CS) nanoparticles (NPs) have a glycan matrix that may be useful for in vivo delivery of proteins. Current procedures for the formation of DS‐CS NPs with incorporated proteins is to first combine DS or CS with the protein of interest and then proceed to particle formation. In general, this process requires a significant amount of protein for particle formation, and after the reaction the unincorporated protein cannot be easily recovered for future incorporation. Considering the high cost and limited availability of various recombinant therapeutic proteins, in this study we investigated whether proteins can be incorporated efficiently in pre‐formed DS‐CS NPs. To do so, DS‐CS NPs were formulated, prepared on a large scale, and lyophilized. The reconstituted DS‐CS NPs were sized 333±16 nm, with a polydispersity of 0.119±0.026 and zeta potential of ‐32.4±1.4 mV. Stromal cell‐derived factor‐1α (SDF‐1α) was loaded onto the DS‐CS NPs at various concentrations. At the ratio of SDF‐1α to DS of 0.02:1, 85±8 % of the loaded SDF‐1α was incorporated in the NPs. The resulted particles (SDFNPs) had a diameter of 393±17 nm, a polydispersity of 0.147±0.032, and a zeta potential of ‐28.6±1.9 mV. The incorporated SDF‐1α had the same chemotactic activity as that of free SDF‐1α. Administration of aerosolized SDFNP to the lungs of rats showed that ~ 30% SDF‐1α remained in the tissue at 72 hr after the delivery, while free SDF‐1α was mostly cleared from the lung (~97%) after 16 hr. This study shows that pre‐formed DS‐CS NPs incorporated SDF‐1α with high efficiency, and can be a useful vehicle for delivery of recombinant therapeutic proteins to the lung parenchyma.