PEGylated Triacontanol Substantially Enhanced the Pharmacokinetics of Triacontanol in Rats

Abstract

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 versus 9 × 10 g·L), body residence (MRT, 9.40 ± 2.03 h versus 2.59 ± 0.705 h, p < 0.001), and systemic exposure (AUC 29.1 ± 5.33 μM·h versus 0.529 ± 0.248 μM·h, p < 0.001) of TA were all significantly increased compared to pristine TA. When intravenously administered (6.85, 22.8, and 68.5 μmol·kg) in rats, PEGylated TA exhibited a slow clearance (44.8 ± 8.62, 47.9 ± 5.18, and 46.9 ± 16.5 mL·h·kg), long elimination half-life (8.76 ± 0.96, 10.4 ± 1.66, and 11.1 ± 2.81 h), and abundant systemic exposure (AUC, 155 ± 24.2, 523 ± 56.2, and 1709 ± 245 μM·h). Meanwhile, its metabolite TA showed a high AUC (28.4 ± 5.14, 151 ± 25.4, and 797 ± 184 μM·h) and slow elimination ( t, 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.

Optimization and modeling of PEGylated, hydrocortisone‐17‐butryate‐loaded poly(lactic‐co‐glycolic acid) microspheres

“…However, the effects of PEGylation on corticosteroid release and overall characteristics of PLGA nanospheres has not been quantified and accurately computationally modeled. [15][16][17][18] Therefore it is proposed, through formulation optimization and modeling this corticosteroid delivery platform can extend therapeutic duration, alleviate high corticosteroid concentration effects, and be more effectively dosed through application of a biphasic release model for the PEGylated nanocarriers.…”

PEGylation of Chrysin Improves Its Water Solubility while Preserving the In Vitro Biological Activity

“…PEGylation of low-molecular-weight natural products has scarcely been reported. Some examples of PEGylated natural products include PEGylated curcumin, astaxanthin, triancontanol, and solanesol . The PEGylation of chrysin using 1 and 2 kDa mPEGs has also been published, with the aim of obtaining nanoparticles for doxorubicin (Dox) encapsulation and delivery .…”

Self-assembly of 1-triacontanol onto layered doubled hydroxide nano-carriers toward sustainable growth regulation of maize

“…Since the physiological activity has been first discovered by Ries et al in alfalfa, the yield and quality increasing effect of 1-triacontanol on Artemisia annua , tomato, rice and many other agronomic, horticultural, medicinal and aromatic plants has been reported. 9,10 Through spraying on leaves and transportation within the plants, colloidally dispersed 1-triacontanol can regulate physiological behaviours including photosynthesis, nitrogen fixation and enzyme activities. 11–13 In most relevant laboratory research, 1-triacontanol was dissolved in organic solution and dispersed in water with lots of surfactants by random morphology or size distribution, while its successful application in a pure water system by regular morphology and size has been rarely reported.…”