TY - JOUR
T1 - Real-Time Label-Free Targeting Assessment and in Vitro Characterization of Curcumin-Loaded Poly-lactic-co-glycolic Acid Nanoparticles for Oral Colon Targeting
AU - Akl, Mohamed A.
AU - Kartal-Hodzic, Alma
AU - Suutari, Teemu
AU - Oksanen, Timo
AU - Montagner, Isabella Monia
AU - Rosato, Antonio
AU - Ismael, Hatem R.
AU - Afouna, Mohsen I.
AU - Caliceti, Paolo
AU - Yliperttula, Marjo
AU - Samy, Ahmed M.
AU - Mastrotto, Francesca
AU - Salmaso, Stefano
AU - Viitala, Tapani
N1 - Funding Information:
This research was funded by Center for International Mobility CIMO, Egypt (grant #KM-14-9066) and Academy of Finland (grant #s 137053 and 263861) and partly supported by grants from the Finnish Cultural Foundation to A.K.-H., and the Italian Association for Cancer Research (AIRC, IG-17035 and Special Program Molecular Clinical Oncology 5 per mille ID 10016), and Progetto di Ricerca di Ateneo 2015, University of Padova, to AR.
Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/10/15
Y1 - 2019/10/15
N2 - 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 gastro-intestinal 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 bilayers 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- A nd 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 of 7.3 ± 0.3, 13.5 ± 1.0, 27.3 ± 4.9, and 26.0 ± 1.3 μg per 104 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- A nd GE11-coated C-PLGA NPs displayed high potential for application as active targeted carriers for anticancer drug delivery to the colon.
AB - 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 gastro-intestinal 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 bilayers 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- A nd 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 of 7.3 ± 0.3, 13.5 ± 1.0, 27.3 ± 4.9, and 26.0 ± 1.3 μg per 104 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- A nd GE11-coated C-PLGA NPs displayed high potential for application as active targeted carriers for anticancer drug delivery to the colon.
UR - http://www.scopus.com/inward/record.url?scp=85073036067&partnerID=8YFLogxK
U2 - 10.1021/acsomega.9b02086
DO - 10.1021/acsomega.9b02086
M3 - Article
AN - SCOPUS:85073036067
SN - 2470-1343
VL - 4
SP - 16878
EP - 16890
JO - ACS Omega
JF - ACS Omega
IS - 16
ER -