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 the cleavage of the backbone structure. When the cleavage occurs at the cross-linking point, the hydrogel elutes as an original polymer unit, i.e., four-armed 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 essential. This paper investigates time-wise diffusion from the skin, biodistribution to distant organs, and clearance of fluorescence-labeled four-armed PEGs with molecular weight (Mw) 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 Mw-dependent. Four-armed PEGs with Mw less than or equal to 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 Mw greater than or equal to 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 Mw-dependent 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

“…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). 22 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. The molecular mobility seems to proceed in two distinct phases, as observed with 20 and 35 kDa PEO (Figure 4B).…”

“…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. 22 The distribution of PEO molecules into the kidney and subsequent glomerular filtration are influenced by their M w . 25−27 According to the estimated size limit of glomerular filtration pores in mice (approximately 4−6 nm), macromolecules smaller than this size are more likely to pass through the pores, accumulate, and be filtered into the urine.…”

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

“…1−3 Characterizing the molecular weight provides valuable insights into the properties of polymers. 4,5 In the case of conventional polymers, gel permeation chromatography is commonly used to directly measure molecular weight with precision 6,7 However, this method is not suitable for supramolecular polymers, which are a distinct type of polymer formed through noncovalent interactions. 8−12 Unlike covalent polymers, supramolecular polymers exhibit dynamic behavior, and their formation is highly dependent on concentration.…”