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Blood Compatibility of Cetyl Alcohol/Polysorbate-Based Nanoparticles

Purpose

Pegylated and nonpegylated cetyl alcohol/polysorbate nanoparticles (E78 NPs) are being tested as drug carriers for specific tumor and brain targeting. Because these nanoparticle formulations are designed for systemic administration, it is important to test the compatibility of these lipid-based NPs with blood and blood cells.

Methods

The hemocompatibility of E78 NPs was evaluated with a particular focus on hemolytic activity, platelet function, and blood coagulation. Human red blood cell lysis was determined by measuring hemoglobin release. Activation and aggregation of human platelets were determined using flow cytometry and aggregometry, respectively. Finally, the whole blood clotting time was measured using human blood.

Results

E78 NPs did not cause in vitro red blood cell lysis at concentrations up to 1 mg/mL. In addition, under conditions tested, E78 and polyethylene glycol (PEG)-coated E78 NPs (PEG-E78 NPs) did not activate platelets. In fact, both NP formulations very rapidly inhibited agonist-induced platelet activation and aggregation in a dose-dependent manner. Additionally, E78 NPs significantly prolonged in vitro whole blood clotting time at a concentration of 500 μg/mL or greater.

Conclusions

It was concluded that PEG-coated and nonpegylated E78 NPs have potential blood compatibility at clinically relevant doses. Based on the calculated nanoparticle-to-platelet ratio, the concentration at which E78 NPs could potentially affect platelet function in vivo was approximately 1 mg/mL.

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Koziara, J.M., Oh, J.J., Akers, W.S. et al. Blood Compatibility of Cetyl Alcohol/Polysorbate-Based Nanoparticles. Pharm Res 22, 1821–1828 (2005). https://doi.org/10.1007/s11095-005-7547-7

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  • DOI: https://doi.org/10.1007/s11095-005-7547-7

Key Words

  • blood clotting
  • hemocompatibility
  • platelet activation
  • platelet aggregation
  • platelets
  • red blood cell lysis