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    Real-Time Label-Free Targeting Assessment and in Vitro Characterization of Curcumin-Loaded Poly-lactic-co-glycolic Acid Nanoparticles for Oral Colon Targeting

    Year: 2019

    Journal: ACS Omega, Volume 4, OCT 15, page 16878–16890

    Authors: Akl, Mohamed A.; Kartal-Hodzic, Alma; Suutari, Teemu; Oksanen, Timo; Montagner, Isabella Monia; Rosato, Antonio; Ismael, Hatem R.; Afouna, Mohsen, I; Caliceti, Paolo; Yliperttula, Marjo; Samy, Ahmed M.; Mastrotto, Francesca; Salmaso, Stefano; Viitala, Tapani

    The exploitation of curcumin for oral disease treatment is limited by its low solubility, poor bioavailability and low stability. Surface-functionalized Poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) have shown promising results to ameliorate selective delivery of drugs to the gastrointestinal tract. In this study, curcumin-loaded PLGA NPs (C-PLGA NPs) of about 200 nm were surface-coated with chitosan (CS) for gastro-intestinal mucosa adhesion, wheat germ agglutinin (WGA) for colon targeting or GE11 peptide for tumor colon targeting. Spectrometric and zeta potential analyses confirmed the successful functionalization of the C-PLGA NPs. Real-time label-free assessment of the cell membrane-NP interactions and NP cell uptake were performed by quartz crystal microbalance coupled with supported lipid Mayers and by surface plasmon resonance coupled with living cells. The study showed that CS-coated C-PLGA NPs interact with cells by the electrostatic mechanism, while both WGA- and GE11-coated C-PLGA NPs interact and are taken up by cells by specific active mechanisms. In vitro cell uptake studies corroborated the real-time label-free assessment by yielding a curcumin cell uptake 7.3 +/- 0.3, 13.5 +/- 1.0, 27.3 +/- 4.9, and 26.0 +/- 1.3 mu g per 10(4) HT-29 cells for noncoated, CS-, WGA-, and GE11-coated C-PLGA NPs, respectively. Finally, preliminary in vivo studies showed that the WGA-coated C-PLGA NPs efficiently accumulate in the colon after oral administration to healthy Balb/c mice. In summary, the WGA- and GE11-coated C-PLGA NPs displayed high potential for application as active targeted carriers for anticancer drug delivery to the colon.
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