Development of a PEG Derivative Containing Hydrolytically Degradable Hemiacetals.
Development of a PEG Derivative Containing Hydrolytically Degradable Hemiacetals.
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开发含有水解降解半叶子的PEG衍生物。
DOI：
10.1021/ma1020648
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发表时间：
2010-12-14
期刊：
影响因子：
5.5
通讯作者：
Elisseeff J
中科院分区：
文献类型：
--
作者：
Reid B;Tzeng S;Warren A;Kozielski K;Elisseeff J
Synthetic polymers are ubiquitous in the biomedical sciences, with applications in drug delivery, medical devices, and artificial matrices for tissue engineering. 1-4 Since the success of the first synthetic poly (glycolic acid)-based suture in the 1960’s, vast effort has been devoted to designing synthetic biodegradable polymers. 5 Given the complexity of regenerative medicine, there is a need to tailor biomaterials for specific applications. 6 Among the hydrophilic synthetic polymers, poly (ethylene glycol)(PEG) is a widely used material due to its resistance to protein adsorption and its biocompatiblity. 7 PEG and PEG-copolymers play critical roles ranging from PEGylation therapeutics to hydrogel scaffolds mimicking the natural extracellular matrix for cell culture and tissue regeneration. PEG, or poly (ethylene oxide) PEO with molecular weight exceeding 20 kDA, is a hydrolytically non-degradable polymer with excellent solubility in water and various organic solvents. 8 As a result of PEG’s non-degradability, the entire polymer chain is excreted through the kidneys (< 30 kDa) or through the liver (> 30 kDa). 9 Therefore, only PEG of molecular weight less than 50 kDa is typically used in biomedical applications to ensure elimination from the body. 10 To overcome this limitation, efforts have been made to introduce biodegradability into PEG or to make copolymers of PEG and biodegradable polymer moieties such as esters. 11, 12 Polyesters, as well as other similarly structured polymers, degrade via hydrolysis and give rise to products with carboxylic acid terminal groups. 13 As a result, their degradation may create an acidic environment that can induce tissue toxicity. 14 In this Communication, we report a synthetic scheme introducing hemiacetals randomly into the backbone of PEG which we will refer to as ROPEG, randomly oxidized PEG. This simple synthetic scheme of incorporating minimal random hemiacetals within the PEG backbone will retain beneficial characteristics of PEG while allowing hydrolytic degradation to non-acidic by-products. 15, 16Utilizing the Fenton reaction of hydrogen peroxide and ferric chloride at a neutral pH we developed a simple method of introducing hemiacetals into the PEG backbone. Previous reports have shown the Fenton reaction to depolymerize PEG but particularly requiring highly acidic conditions to drive the reaction to completion. 17, 18 Almkvist et al. oxidized PEG via hydroxyl radicals generated by Fenton’s reagent (Fe (II)/H2O2) in aqueous solution and demonstrated PEG degradation products of alcohols, aldehydes and formate esters using 1H NMR. 17 This degradation pathway suggests that there are multiple steps of PEG oxidation and degradation into a variety of PEG oligomers, including PEG hemiacetals, an intermediate formed prior to complete depolymerization of the backbone. 17 We found that keeping the pH neutral during the Fenton reaction can oxidize the PEG backbone to
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