Physical Absorption of Folic Acid and Chitosan on Dihydroartemisinin-Loaded Poly-Lactic-Co-Glycolic Acid Nanoparticles via Electrostatic Interaction for Their Enhanced Uptake and Anticancer Effect

Abstract

In this study, dihydroartemisinin (DAR), an anticancer agent with low toxicity, was loaded into poly-lactic-co-glycolic acid (PLGA) nanoparticles. The obtained PLGA cores were then coated with chitosan (CS) and/or folic acid (FA) by electrostatic interactions to enhance their anticancer and cellular uptake properties. DAR-loaded PLGA nanoparticles were prepared by the solvent evaporation method. CS and FA solutions at different ratios were dispersed concurrently into the PLGA suspension to facilitate electrostatic interactions and form nanosuspensions. The physiochemical properties of nanoparticles such as average particle size (Z), polydispersity index (PDI), zeta potential (ZP), TEM image, X-ray diffraction, and encapsulation efficiency were determined. We then determined the role of FA and CS coating on the nanoparticle surface in cytotoxicity, cellular uptake, and apoptosis. We show that the resultant nanoparticles were spherical and uniform, with a coating layer containing FA and CS covering PLGA cores with a Z of 223.5±4.28 nm, PDI of 0.209±0.03, and ZP of 15.75±1.3 mV. Both FA and CS improved the cytotoxicity of nanoparticles compared to free DAR and PLGA nanoparticles in HL-60 and KB cancer cell lines. Further, FA enhanced the cellular uptake of nanoparticles to a greater extent than CS. However, CS contributed more to apoptosis induction than FA.

Design of Chitosan-Coated, Quercetin-Loaded PLGA Nanoparticles for Enhanced PSMA-Specific Activity on LnCap Prostate Cancer Cells

“…The weight loss steps observed correspond with the temperatures of the degradation steps observed by the DSC thermograms (Figure 7A). The loaded nanoparticles exhibit greater thermal stability compared to both the unloaded nanoparticles and pristine polymers, probably due to nanoparticle interactions and intact structural conformation, which is consistent with previous studies with the individual components [37,46,47,51]. For TGA (Figure 6B), weight loss of the nanoparticle systems can be divided into the stages where weight loss is due to the water loss from the chitosan component at 0-300 • C [41] and the thermal degradation stage until 400 • C for the unloaded nanoparticles and 450 • C for the loaded nanoparticles.…”

“…The weight loss steps observed correspond with the temperatures of the degradation steps observed by the DSC thermograms (Figure 7A). The loaded nanoparticles exhibit greater thermal stability compared to both the unloaded nanoparticles and pristine polymers, probably due to nanoparticle interactions and intact structural conformation, which is consistent with previous studies with the individual components [37,46,47,51].…”

“…For the “coated” nanoparticles, the centrifugal pellet was resuspended and incubated in the dark, at room temperature, for 1.5 h, with solutions of chitosan and folic acid. The chitosan solutions were prepared by dissolving chitosan in 1% glacial acetic acid and were subsequently filtered, while the folic acid solutions were prepared by dissolving folic acid in 0.4 M NaOH [ 37 ]. After the incubation period, the nanoparticles were separated by centrifugation and frozen at −80 °C for 24 h. Frozen samples were then lyophilized (Freezone 12 lyophilizer, Labcono, Kansas City, MO, USA) for 24 h. Henceforth, the PLGA nanoparticles are referred to as “uncoated nps”, and the PLGA/chitosan folic acid nanoparticles are referred to as “coated nps”.…”

PLGA-based drug delivery system for combined therapy of cancer: research progress

“…Loading drugs into PLGA micro/nanoparticle directly into tumor cells is a conventional method to increase the bioavailability of drugs to tumor cells and reduce damage to normal tissues [109,126,127]. For killing tumor cells, PLGA micro/nanoparticle usually deliver chemotherapeutics, photothermal preparations or radioactive preparations, and the drug-loaded particles are delivered to the tumor site by in-situ injection or transvascular transport [128].…”

“…In addition, DC, as the most powerful antigen-presenting cell, also has a good absorption capacity for micro/nanoparticles. Presenting antigens by direct or crossover methods promotes the activation of T lymphocytes and produces a cellular immune response dominated by CD8+T cell infiltration, which is the basis of DC as an immunotherapy method [126,140]. However, the immunosuppression in the tumor microenvironment leads to a decrease in the number of DCs and their function is inhibited [156].…”