PEGylated Triacontanol Substantially Enhanced the Pharmacokinetics of Triacontanol in Rats

Triacontanol (TA), a natural compound with various health benefits, is extensively used as a nutritional supplement. The therapeutic and nutraceutical applications of TA are limited due to its poor aqueous solubility. PEGylated triacontanol (PEGylated TA) was designed to improve the solubility and pharmacokinetics of TA. After PEGylation, the solubility (∼250 g·L^–1 versus 9 × 10^–14 g·L^–1), body residence (MRT, 9.40 ± 2.03 h versus 2.59 ± 0.705 h, <i>p</i> < 0.001), and systemic exposure (AUC_0–inf, 29.1 ± 5.33 μM·h versus 0.529 ± 0.248 μM·h, <i>p</i> < 0.001) of TA were all significantly increased compared to pristine TA. When intravenously administered (6.85, 22.8, and 68.5 μmol·kg^–1) in rats, PEGylated TA exhibited a slow clearance (44.8 ± 8.62, 47.9 ± 5.18, and 46.9 ± 16.5 mL·h^–1·kg^–1), long elimination half-life (8.76 ± 0.96, 10.4 ± 1.66, and 11.1 ± 2.81 h), and abundant systemic exposure (AUC_0–<i>t</i>, 155 ± 24.2, 523 ± 56.2, and 1709 ± 245 μM·h). Meanwhile, its metabolite TA showed a high AUC_0–<i>t</i> (28.4 ± 5.14, 151 ± 25.4, and 797 ± 184 μM·h) and slow elimination (<i>t</i>_1/2, 10.1 ± 2.03, 7.78 ± 1.74, and 6.82 ± 0.58 h). Our results demonstrated that PEGylated TA has superior pharmacokinetics, which enhanced its nutritional and pharmacodynamic potency, and thus warrants further investigations