Double pH-responsive supramolecular copolymer micelles based on the complementary multiple hydrogen bonds of nucleobases and acetalated dextran for drug delivery

Kuang, Huihui; Wu, Yuan; Zhang, Zhiyun; Li, Jizhen; Chen, Xuesi; Xie, Zhigang; Jing, Xiabin; Huang, Yubin

doi:10.1039/c5py00042d

Cited by 30 publications

(33 citation statements)

References 32 publications

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“…26,28,29 (e) Amphiphilic Ac-DEX block copolymers, synthesized by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. 31,32 further conjugation of targeting moieties or polyethylene glycol (PEG) to enhance the stability. [21][22][23][24] Ac-DEX-based copolymers represent another category of functionalized Ac-DEX family.…”

Section: Hélder a Santosmentioning

confidence: 99%

Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications

et al. 2021

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Section: Hélder a Santosmentioning

confidence: 99%

Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications

et al. 2021

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“…We collected NMR spectra on Bruker 600 MHz NMR. Disappearance of anomeric proton peaks at 6.7 ppm and 6.3 ppm, corresponding to the alpha and beta stereoisomers of the anomeric center respectively, demonstrated the complete reduction to the alcohol [50].…”

Section: Methodsmentioning

confidence: 99%

Dextranol: An inert xeroprotectant

2019

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Dextranol, a reduced dextran, prevents damage to stored dry protein samples that unmodified dextran would otherwise cause. Desiccation protectants (xeroprotectants) like the polysaccharide dextran are critical for preserving dried protein samples by forming a rigid glass that protects entrapped protein molecules. Stably dried proteins are important for maintaining critical information in clinical samples like blood serum as well as maintaining activity of biologic drug compounds. However, we found that dextran reacts with both dried serum proteins and lyophilized purified proteins during storage, producing high-molecular weight Amadori-product conjugates. These conjugates appeared in a matter of days or weeks when stored at elevated temperatures (37° or 45°C), but also appeared on a timescale of months when stored at room temperature. We synthesized a less reactive dextranol by reducing dextran’s anomeric carbon from an aldehyde to an alcohol. Serum samples dried in a dextranol-based matrix protected the serum proteins from forming high-molecular weight conjugates. The levels of four cancer-related serum biomarkers (prostate specific antigen, neuropilin-1, osteopontin, and matrix-metalloproteinase 7) decreased, as measured by immunoassay, when serum samples were stored for one to two weeks in dextran-based matrix. Switching to a dextranol-based xeroprotection matrix slightly reduced the damage to osteopontin and completely stopped any detectable damage during storage in the other three biomarkers when stored for a period of two weeks at 45°C. We also found that switching from dextran to dextranol in a lyophilization formulation eliminates this unwanted reaction, even at elevated temperatures. Dextranol offers a small and easy modification to dextran that significantly improves the molecule’s function as a xeroprotectant by eliminating the potential for damaging protein-polysaccharide conjugation.

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“…We collected NMR spectra on Bruker 600 MHz NMR. Disappearance of anomeric proton peaks at 6.7 ppm, and 6.3 ppm, corresponding to the alpha, and beta stereoisomers of the anomeric center, demonstrated the complete reduction to the alcohol (46).…”

Section: Methodsmentioning

confidence: 99%

Dextranol: A better lyoprotectant

Jones¹,

Mahajan²,

Aksan³

2018

Preprint

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19Dextranol, a reduced dextran, prevents damage to stored dry protein samples that unmodified dextran 20 would otherwise cause. Lyoprotectants like the polysaccharide dextran are critical for preserving dried protein 21 samples by forming rigid a glass that protects entrapped protein molecules. Stably dried proteins are important 33 molecule's function as a lyoprotectant by eliminating the potential for damaging protein-polysacharide 34 conjugation.35 41 polysaccharides. Large uncharged polymers like polysaccharides protect proteins by molecular crowding, water 42 replacement, and glass formation (4-8). 43Dextran has frequently been used as a polysaccharide lyoprotectant in dry protein formulations, mainly 44 due to its high glass transition temperature, which enables room temperature storage (4,9,10). As an inert 45 additive (11), dextran is particularly suitable to be used as a preservative in pharmaceutical products (12-17). 46As a result, there have been numerous drugs on the market that contain dextran as a preservative (18,19), 47 including biologics (20,21). 48Dextran has one drawback, discovered in the food science field in early 1990s; storage of proteins with 49 dextran in low-moisture conditions can facilitate formation of protein-dextran conjugates. (22-25). This 50 reaction has been well documented to occur with various proteins (26-30). Dextran is a branched D-glucose 51 polymer by α-1,6 linkages and α-1,3 linkages at branch points with a single reducing end and multiple non-52 reducing ends. The conjugation is formed via a Mailard reaction between dextran's reducing end and protein's 53 primary amines (N-terminus and/or lysine side chains) leading via a Schiff base to the Amadori product. While 54 these conjugates are mostly shown to form at elevated temperatures (≥50°C) over a time period of days, there 55 are reports of protein-sugar conjugates forming even at lower temperatures, typically over longer time scales. 56 (31-36) 57 Dextran-protein conjugates are larger and more soluble than un-modified proteins. The size of dextrans, 58 like proteins, covers the low to high kilodalton range and thus, conjugation can easily double or triple the size 59 of the un-modified protein. Like pegylation, dextran conjugation also increases a protein's solubility (37) and 60 also makes it a better emulsifier (23,38-40). Conjugation of carbohydrates with proteins also causes acidification 61 (lowering of isoelectric point) by removing positive charges from lysine residues (41,42). 62 Dry storage is an attractive alternative to the typical cryogenic storage for stabilization of proteinaceous 63 biomarkers in clinical biofluid samples like blood serum. Many clinical samples are collected each year and 64 stored in archival biobanks for diagnostic and retrospective biomarker discovery research. The ten largest

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Double pH-responsive supramolecular copolymer micelles based on the complementary multiple hydrogen bonds of nucleobases and acetalated dextran for drug delivery

Cited by 30 publications

References 32 publications

Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications

Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications

Dextranol: An inert xeroprotectant

Dextranol: A better lyoprotectant

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