Effects of PEGylation on the physicochemical properties and in vivo distribution of organic nanotubes

Abstract

Application of organic nanotubes (ONTs) into drug nanocarriers ultimately requires validation in live animals. For improving the dispersibility in biological media and in vivo distribution, the outer surface of an ONT was functionalized with polyethylene glycol (PEG) via the coassembly of an ONT-forming lipid with 5–20 mol% of a PEG-tethered lipid analogue (PEG-lipid). Firstly, the effect of PEGylation on the psysicochemical properties of ONTs, such as morphology and dispersibility, was investigated. PEGylation of ONTs slightly reduced the average length and effectively prevented the aggregation in phosphate-buffered saline (PBS). The PEGylated ONTs even showed high thermal stability in aqueous dispersion at least up to 95°C. Secondly, differential scanning calorimetry and powder X-ray diffraction indicated that ~10 mol% of PEG-lipid was completely incorporated into the ONTs, while 20 mol% of PEG-lipid encountered a partial phase separation during coassembly. In the heating differential scanning calorimetry runs, the resultant PEGylated ONTs with 5 mol% PEG-lipid showed no sign of phase separation up to 180°C under lyophilized condition, while those with 10 mol% and 20 mol% PEG-lipid showed some phase separation of the PEG-lipid above 120°C. Finally, PEGylation significantly affected the tissue distribution and prolonged the persistence time in the blood in mice. Non-PEGylated ONTs was quickly cleared from the circulation after intravenous infusion and preferentially accumulated in the lung, while PEGylated ONTs was mainly trapped in the liver and could circulate in the blood up to 24 hours. This study provided valuable information of physicochemical properties and the in vivo distribution behavior of PEGylated ONTs for their potential application into drug nanocarriers.

Lipid Nanotube Tailored Fabrication of Uniquely Shaped Polydopamine Nanofibers as Photothermal Converters

“…In PBS buffer, however, the PDA‐LNT‐2 aggregated into large particles. This aggregation phenomenon was the same with original LNT‐2 in PBS buffer, the salt ions in which shielded the surface charge and caused the aggregation of the hybrids . In contrast, no severe aggregation was observed for the PDA‐LNT‐1 in the buffer (Figure S8 in the Supporting Information).…”

Integrin‐Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor‐Specific Delivery Achieve MYCN Silencing with Improved Survival

“…PEGylated cationic and anionic nanocomplexes were stable in PBS at ≈205 nm and ≈147 nm, respectively (Figure 1B ), demonstrating the anticipated shielding effect of this PEGylation strategy. [ 13 , 18 ]…”

Preparation, optimization, and pharmacokinetic study of nanoliposomes loaded with triacylglycerol‐bound punicic acid for increased antihepatotoxic activity

“…Dynamic light scattering method was used to evaluate the droplet size distribution of TPAR‐NL, PDI, and z‐potential as described in earlier report with slight modifications (Gibis, Zeeb, & Weiss, ). The diluted TPAR‐NL (1:50 v/v) in DDW (Ding, Minamikawa, Kameta, & Shimizu, ) was characterized ( n = 3) using Brookhaven‐90 Plus (PALS) instrument (Brookhaven Instruments Corp., Holtsville, NY). Similarly, the physical stability of TPAR‐NL was also evaluated by measuring the appropriate indices on the first, second, third, and fourth week after preparation and storage over a 1‐month period at 4 °C.…”