Influence of Structural Features on the Cellular Uptake Behavior of Non-Targeted Polyester-Based Nanocarriers

Macromol Biosci. 2016 Nov;16(11):1643-1652. doi: 10.1002/mabi.201600138. Epub 2016 Jul 27.

Abstract

The development of delivery systems efficiently uptaken by cells is of due importance since sites of drug action are generally localized in subcellular compartments. Herein, naked and core-shell polymeric nanoparticles (NPs) have been produced from poly(lactic-co-glycolic acid)-PLGA, poly(ethylene oxide)-b-poly(ε-caprolactone)-PEO-b-PCL, and poly(ethylene oxide)-b-poly(lactic acid)-PEO-b-PLA. The nanostructures are characterized and the cellular uptake behavior is evaluated. The data evidence that cellular uptake is enhanced as the length of the hydrophilic PEO-stabilizing shell reduces and that high negative surface charge restricts cellular uptake. Furthermore, NPs of higher degree of hydrophobicity (PEO-b-PCL) are more efficiently internalized as compared to PEO-b-PLA NPs. Accordingly, taking into account our recent published results and the findings of the current investigation, there should be a compromise regarding protein fouling and cellular uptake as resistance to nonspecific protein adsorption and enhanced cellular uptake are respectively directly and inversely related to the length of the PEO-stabilizing shell.

Keywords: cellular uptake; confocal microscopy; flow cytometry; light scattering; polymeric nanoparticles.

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Lactic Acid / chemistry
  • Lactic Acid / pharmacokinetics
  • Lactic Acid / pharmacology
  • Nanoparticles / chemistry*
  • Polyesters* / chemistry
  • Polyesters* / pharmacokinetics
  • Polyesters* / pharmacology
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacokinetics
  • Polyethylene Glycols / pharmacology
  • Polyglycolic Acid / chemistry
  • Polyglycolic Acid / pharmacokinetics
  • Polyglycolic Acid / pharmacology
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Structure-Activity Relationship

Substances

  • Polyesters
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • polycaprolactone
  • Polyglycolic Acid
  • Lactic Acid
  • Polyethylene Glycols