Effects of amphiphilic star-shaped poly(ethylene glycol) polymers with a cholic acid core on human red blood cell aggregation

Abstract

Elevated red blood cell (RBC) aggregation increases low-shear blood viscosity and is closely related to several pathophysiological diseases such as atherosclerosis, thrombosis, diabetes, hypertension, cancer, and hereditary chronic hemolytic conditions. Non-ionic linear polymers such as poly(ethylene glycol) (PEG) and Pluronic F68 have shown inhibitory effects against RBC aggregation. However, hypersensitivity reactions in some individuals, attributed to a diblock component of Pluronic F68, have been reported. Therefore, we investigated the use of an amphiphilic star-shaped PEG polymer based on a cholic acid core as a substitute for Pluronics to reduce RBC aggregation. Cholic acid is a natural bile acid produced in the human liver and therefore should assure biocompatibility. Cholic acid based PEG polymers, termed CA(PEG)4, were synthesized by anionic polymerization. Size exclusion chromatography indicated narrow mass distributions and hydrodynamic radii less than 2 nm were calculated. The effects of CA(PEG)4 on human RBC aggregation and blood viscosity were investigated and compared to linear PEGs by light transmission aggregometry. Results showed optimal reduction of RBC aggregation for molar masses between 10–16 kDa of star-shaped CA(PEG)4 polymers. Cholic acid based PEG polymers affect the rheology of erythrocytes and may find applications as alternatives to linear PEG or Pluronics to improve blood fluidity.

Erythrocyte rheological properties but not whole blood and plasma viscosity are associated with severity of hypertension in older people

“…Moreover, epidemiological studies have recognized erythrocyte aggregation to be a strong cardiovascular risk factor [21]. Erythrocyte aggregability increases with the severity of venous insufficiency [22].…”

Paclitaxel-loaded star-shaped copolymer nanoparticles for enhanced malignant melanoma chemotherapy against multidrug resistance

“…It is an excipient that overcomes multidrug resistance and a P-glycoprotein (P-gp) inhibitor that augments the oral bioavailability and cytotoxicity of anticancer drugs 23–25. CA, which is the main bile acid in human body, was selected as the poly-hydroxy initiator due to good biocompatibility 26. PLGA, TPGS, and CA have been approved by the US Food and Drug Administration and used in pharmaceutical products 9,27…”

Delivery of Drugs Bound to erythrocytes: New Avenues for an Old Intravascular Carrier

“…In saline, and the maximum amount of HPG-C18-PEG adsorbed onto RBCs was greater than in plasma, due to the interactions between the polymer and plasma proteins (e.g., albumin). Janvier et al reported that the use of amphiphilic star-shaped PEG polymers (four chains of PEG) with a cholic acid core with masses between 10–16 kDa efficiently reduced RBCs aggregation [265]. Unlike Pluronic F68, a PEG-PPG-PEG triblock copolymer that can also decrease RBC aggregation, the use of cholic acid as the core group did not induce any adverse reactions.…”