Dependence of pharmacokinetics and biodistribution on polymer architecture: effect of cyclic versus linear polymers

Abstract

The ability of a polymer to reptate through a nanopore has an influence on its circulatory half-life and biodistribution, since many physiological barriers contain nanopores. A cyclic polymer lacks chain ends, and therefore, cyclic polymers with molecular weights greater than the renal threshold for elimination should circulate longer than their linear-polymer counterparts when injected into animals. As predicted, radiolabeled cyclic polymers with molecular weights greater than the renal threshold have longer blood circulation times in mice than do linear polymers of comparable molecular weight.

Figure 1

NMR (¹H, 400 MHz) of A) Linear and B) Cyclic Phenol containing PEG(2 kD)-g-PCL(9 kD).

Figure 2

Linear and cyclic polymer concentration in the blood with respect to time.

Figure 3

Biodistribution of linear and cyclic polymer A–B) 32 kD, C–D) 50 kD and E–F) 90 kD in mice at 24 h, plotted as % injected dose per gram of tissue versus time (left panel, urine and feces were calculated by dividing % injected dose with animal weight) and % injected dose per organ versus time (right panel). Error bars have been omitted from the feces and urine values because the respective excrements for each time point were not collected individually but were pooled together. The % recovery of linear and cyclic polymer with 32, 50 and 90 kD are 80.2, 68.3, 72.8, 76.9, 69.8 and 61.4, respectively.