In vivo biological evaluation of high molecular weight hyperbranched polyglycerols

Abstract

Hyperbranched polyglycerols (HPGs) are water-soluble polyether polyols that can be synthesized in a controlled manner with low polydispersity. Recently we reported the synthesis and characterization of very high molecular weight and narrowly polydispersed HPGs that could be used as potential alternatives to high generation dendrimers, their advantage being the relative simplicity of synthesis. Reported in this article are the pharmacokinetic properties of these polymers. Two polymers of number average molecular weights 106,000 and 540,000 were tested in mice for their pharmacokinetic behavior. The plasma half-life for the lower molecular weight polymer was around 32 h whereas that of the higher molecular weight HPG was approximately 57 h. Our results show that these high molecular weight HPGs, which can be prepared in a single step reaction, are potential candidates for drug delivery and imaging applications where a long circulating polymer is highly desirable. A detailed tissue distribution profile of these polymers as a function of molecular weight is described. These polymers were also found to be hydrolytically stable and the concentration dependence of solution viscosity measurements suggested the absence of any aggregation.

Glycerol based polyether-nanogels with tunable properties via acid-catalyzed epoxide-opening in miniemulsion

“…Compared to the hPGs with DB values of 0.5-0.6 and intrinsic viscosity of 2.2 mL/g reported by Brooks, nanogel 1 exhibited a lower viscosity although the particles were much larger in size [7]. One of the potential uses of this class of nanogel is as plasma expanders which are typically infused at higher concentrations [35]. Nanogels with low degrees of branching, like nanogels 5 and 7, show similar viscosities as linear PEG, which can be attributed to entanglements [25].…”

“…The absence of entanglements is expected to lead to lower viscosities as compared to linear polymers. Furthermore, the nanogels could be applied at high concentration without a dramatic increase of the solution viscosity -this property is of great biomedical importance [35].…”

Hyperbranched aliphatic polyether polyols

“…119 A detailed tissue distribution profile of these polymers as a function of molecular weight was described by Kainthan and Brooks. 120 Tissue accumulation was found to decrease with time in the kidney, lung, and heart. However, the nonexcreted hbPG is accumulated in the liver and spleen for at least 30 days due to the limited urinary excretion and the nondegradability of the polyether structure.…”

Article Commentary: Hyperbranched Polyglycerol: A Future Alternative to Polyglucose in Peritoneal Dialysis Fluids?

“…Actually, it seems that HPG molecules of high M w (higher than 3 kDa) tend to accumulate in the reticuloendothelial system over time (19). Perhaps HPG solutions should be used for only a single daily dwell.…”