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Download fileCross-linked Histone as a Nanocarrier for Gut Delivery of Hydrophobic Cargos
journal contribution
posted on 04.06.2021, 05:43 authored by Moustafa
T. Mabrouk, Huijuan Zhang, Asmaa A. Zidan, Hailey I. Kilian, Wei-Chiao Huang, Dushyant Jahagirdar, Joaquin Ortega, Jun Xia, Jonathan F. LovellDelivering hydrophobic molecules
through the intestine can be challenging
due to limited cargo solubility and the harsh biochemical environment
of the stomach. Here, we show that a protein-based nanocarrier system
based on the abundant protein histone and the natural cross-linker
genipin can deliver hydrophobic cargos, such as dyes and therapeutic
molecules, through the gastrointestinal tract. Using hydrophobic near-infrared
dyes as model cargos, a panel of potential protein carriers was screened,
and histone was identified as the one with the best loading capability.
The resulting nanoparticles had a positive ζ potential and were
mucoadhesive. Cross-linking of the amine-rich nanocarrier with genipin
was particularly effective relative to other proteins and increased
the stability of the system during incubation with pepsin. Cross-linking
was required for successful delivery of a hydrophobic dye to the colon
of mice after oral gavage. To assess the platform for therapeutic
delivery, another hydrophobic model compound, curcumin, was delivered
using cross-linked histone nanoparticles in a murine colitis model
and significantly alleviated the disease. Taken together, these results
demonstrate that histone is a cationic, mucoadhesive, and cross-linkable
protein nanocarrier that can be considered for oral delivery.
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Keywords
Cross-linkingmucoadhesiveprotein carriersprotein-based nanocarrier systemnear-infrared dyesmodel compoundmurine colitis modelcargo solubilityamine-rich nanocarriermoleculemodel cargosprotein histoneloading capabilityCross-linked HistoneHydrophobic Cargos Deliveringcross-linked histone nanoparticlesGut Deliverycross-linkable protein nanocarriercross-linker genipin