Molecular Weight-Dependent Diffusion, Biodistribution, and Clearance Behavior of Tetra-Armed Poly(ethylene glycol) Subcutaneously Injected into the Back of Mice

Abstract

Four-armed poly(ethylene glycol) (PEG)s are essential hydrophilic polymers extensively utilized to prepare PEG hydrogels, which are valuable tissue scaffolds. When hydrogels are used in vivo, they eventually dissociate due to cleavage of the backbone structure. When the cleavage occurs at the cross-linking point, the hydrogel elutes as an original polymer unit, i.e., fourarmed PEG. Although four-armed PEGs have been utilized as subcutaneously implanted biomaterials, the diffusion, biodistribution, and clearance behavior of four-armed PEG from the skin are not fully understood. This paper investigates time-wise diffusion from the skin, biodistribution to distant organs, and clearance of fluorescence-labeled four-armed PEGs with molecular weight (M w ) ranging from 5−40 kg/mol subcutaneously injected into the back of mice. Changes over time indicated that the fate of subcutaneously injected PEGs is M w -dependent. Four-armed PEGs with M w ≤ 10 kg/mol gradually diffused to deep adipose tissue beneath the injection site and distributed dominantly to distant organs, such as the kidney. PEGs with M w ≥ 20 kg/mol stagnated in the skin and deep adipose tissue and were mainly delivered to the heart, lung, and liver. The fundamental understanding of the M wdependent behavior of four-armed PEGs is beneficial for preparing biomaterials using PEGs, providing a reference in the field of tissue engineering.

Molecular Retention Limitations for Prevascularized Subcutaneous Sites for Islet Transplantation

“…Furthermore, the accumulation of the 20 and 35 kDa PEO molecules in both organs at both time points were significantly lower than 10 kDa PEO (Figure K,L: p < 0.001), supporting the conclusion that the boundary of the prevascularized subcutaneous site limits the mobility of these molecules. Our results are consistent with a prior observation that Alexa fluor-labeled PEO subcutaneously administered to mice easily disappears from the skin and is primarily eliminated through the kidneys when the M w is <10 kDa …”

“…The observed differences in clearance profiles highlight the effectiveness of the prevascularized subcutaneous site’s boundary in restricting the movement of larger molecular species. Previously, an Alexa Fluor 594 labeled PEO with M w of 40 kDa injected into an unmodified subcutaneous site exhibited a rapid decline in fluorescence signal within 1 h (i.e., ∼36% reduction) . In contrast, the results obtained from our study indicated comparatively lower clearance rates for PEO with a M w of ∼35 kDa when administered into the prevascularized subcutaneous site.…”

Indocyanine Green‐Glycogen Conjugates for Near‐Infrared‐Triggered Photothermal Cancer Therapy

“…To date, a variety of synthetic organic nanoparticles such as liposomes, block copolymer micelles, and silica nanoparticles have been utilized for physical encapsulation or covalent conjugation of organic dyes. [21][22][23][24][25][26][27][28] While highly efficient photothermal therapy has been observed in small animal models using these NIR-sensitive nanoparticle systems, the introduction of synthetic nanoparticles has the potential to elicit unwanted immune responses and toxicity, hampering their promise in clinical translation. [29,30] Therefore, developing biocompatible and non-toxic nanocarriers for NIR dyes would be highly desired for photothermal therapy applications.…”

Fluorescence Lifetime-Based Characterization for Supramolecular Polymer Molecular Weight

“…The molecular weight of polymers has a profound impact on their functional performance, physical properties, and processing characteristics. − Characterizing the molecular weight provides valuable insights into the properties of polymers. , In the case of conventional polymers, gel permeation chromatography is commonly used to directly measure molecular weight with precision , However, this method is not suitable for supramolecular polymers, which are a distinct type of polymer formed through noncovalent interactions. − Unlike covalent polymers, supramolecular polymers exhibit dynamic behavior, and their formation is highly dependent on concentration. − Supramolecular polymers exhibit a dynamic nature attributed to the presence of noncovalent interactions, which play a pivotal role in their assembly from monomeric units. Consequently, the formation of supramolecular polymers is highly dependent on concentration. − At lower concentrations, cyclic assemblies or oligomers prevail as the predominant species, while supramolecular polymers emerge at higher concentrations.…”