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 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>Z</mml:mi></mml:math>), 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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>Z</mml:mi></mml:math> of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mn>223.5</mml:mn><mml:mo>±</mml:mo><mml:mn>4.28</mml:mn><mml:mtext> </mml:mtext><mml:mtext>nm</mml:mtext></mml:math>, PDI of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mn>0.209</mml:mn><mml:mo>±</mml:mo><mml:mn>0.03</mml:mn></mml:math>, and ZP of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mn>15.75</mml:mn><mml:mo>±</mml:mo><mml:mn>1.3</mml:mn><mml:mtext> </mml:mtext><mml:mtext>mV</mml:mtext></mml:math>. 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.