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

Abstract

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- 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 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- and GE11-coated C-PLGA NPs displayed high potential for application as active targeted carriers for anticancer drug delivery to the colon.

Orally Administrable Therapeutic Nanoparticles for the Treatment of Colorectal Cancer

“…Glutaraldehyde cross-linking and positive charge of WGA-EF-NP results in smaller particle size and better stability in vitro and in vivo compared with EF-NP. Akl et al (2019) designed curcumin-loaded PLGA NPs (C-PLGA NPs), and coated them with chitosan (CS), WGA and EGF analog peptides (GE11). Chitin promoted interaction of nanoparticles with cancer cells through non-specific electrostatic interactions, whereas WGA and GE11 promoted active targeting and specific recognition of cancer cells.…”

Developing Actively Targeted Nanoparticles to Fight Cancer: Focus on Italian Research

“…The NP surface was decorated with CHIT via coulombic interaction, since it is a polycationic mucoadhesive polysaccharide that adsorbs onto the negatively charged PLGA surface, and via covalent linkage for wheat germ agglutinin and GE11. Results showed that, depending on the coating, NPs were taken up by the cells via different mechanisms, notably by electrostatic interaction for CHIT and specific active mechanisms for both wheat germ agglutinin and GE11 [ 73 ]. GE11-PLGA NPs were also obtained via the nanoprecipitation of a blend (1:1 weight ratio) of two different PLGA-based polymers.…”

“…Scale bar = 200 nm. (A) Uncoated CUR-PLGA NPs, (B) 1% CHIT-CUR-PLGA NPs, (C) wheat germ agglutinin-CUR-PLGA NPs and (D) GE11-CUR-PLGA NPs [ 73 ]. Permitted reproduction under the terms and conditions of the Creative Commons Attribution (CC BY) license ( , accessed on 15 May 2021).…”

Molecular Structure, Interactions and Antimicrobial Properties of Curcumin-PLGA Complexes – A DFT Study

“…The combination of curcumin and PLGA in the complex form was studied both experimentally [17][18][19][20][21][22][23][24] and theoretically [25][26][27]. Earlier, Mukerjee et al have studied the curcumin-loaded PLGA for cancer therapy using experimental techniques.…”

“…They found that PLGAbased drug delivery systems are promising particularly for wound healing activity [19]. More recently, Akl et al have studied curcumin-loaded PLGA nanoparticles for oral colon targeting and they found that CScoated CPLGA nanoparticles can form electrostatic interaction with the cells [23]. From the above literature, we have concluded that the curcumin-loaded PLGA compound is used in many cancer therapy applications as well as antimicrobial, antioxidant, anti-infective, and anti-in ammatory, activities.…”