Cell response to PEGylated poly(dopamine) coated liposomes considering shear stress

Boon M. Teo, Rebecca Van Der Westen, Leticia Hosta-Rigau, Brigitte Städler

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29 Citations (Scopus)

Abstract

Background Liposomes have gained immerse attention in the field of drug delivery as carriers of therapeutic molecules. Their modification with a polymer either to make them stealth (e.g. using PEG) and/or more stable (e.g. using poly(dopamine) (PDA)) is a crucial aspect to improve their performance e.g. the blood circulation time. Despite their potential, there are only a few commercialized liposome-based formulations for intravenous drug delivery. Hence, there is still considerable need to address the challenges involved in the design and characterization of liposomal therapeutics. In the latter case, it is of paramount importance to consider the dynamic in vivo environment, e.g. the interstitial fluidic pressure in tumors, blood flow, or bile flow in the liver. Methods The PEGylation of PDA films was characterized by quartz crystal microbalance with dissipation monitoring, and the optimized protocol was used to assemble PEGylated PDA coated liposomes (LPDA-PEG). Dynamic light scattering, a plate reader, a flow cytometer and a cytotoxicity assay were used to characterize the liposomes and quantify cellular association/uptake and cell viability in the presence and absence of shear stress after 30 min and 4 h. The immortalized skeletal mouse myoblast (C2C12) cell line was chosen as model cancer cells, and a hepatic cell line (HepG2) was selected due to their importance in nanosized drug carrier clearance from the system in the liver. Results The presence of hydrophilic cargo did not affect the PDA assembly process. In the absence of shear stress, there was no difference in cellular uptake/association of both PDA coated liposomes (LPDA) and L PDA-PEG for hepatocytes while myoblasts preferentially internalized/associated with LPDA. In the presence of shear stress, hepatocytes preferentially internalized/associated with LPDA after 30 min, while there was only a significant difference for myoblasts after 4 h. The cell viability remained unaffected in all cases. Conclusions L PDA-PEG are a promising platform towards drug delivery. The nature of cells and fluidic flow are important factors to be considered in their characterization using cell cultures. General significance These findings will contribute in the better understanding of polymer coated liposomes with cells. The importance of microfluidics in cell culture based characterization is demonstrated, and this will eventually affect the way advanced drug delivery vehicles are designed and characterized prior to animal experiments.

Original languageEnglish
Pages (from-to)4838-4847
Number of pages10
JournalBiochimica et Biophysica Acta. General Subjects
Volume1830
Issue number10
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • Liposomes
  • Microfluidics
  • PEGylated liposomes
  • Polydopamine
  • Shear stress

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