Degradable and biocompatible aldehyde-functionalized glycopolymer conjugated with doxorubicin via acid-labile Schiff base linkage for pH-triggered drug release

Xiao, Naiyu; Liang, Hui; Lu, Jiang

doi:10.1039/c1sm06181j

Cited by 55 publications

(57 citation statements)

References 40 publications

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“…Coupling of radical ring-opening polymerization (rROP) of cyclic ketene acetals (CKAs) with CRP techniques including atom transfer radical polymerization (ATRP) 28,29 , nitroxide mediated polymerization (NMP) 30 , RAFT polymerization and macromolecular design via interchange of xanthates (MADIX) 31–33 has led to polymer backbones that are degradable. These CKA polymers have been covalently conjugated to drugs 34 . However to our knowledge degradable CKA polymers prepared by CRP have not been covalently attached to proteins.…”

Section: Introductionmentioning

confidence: 99%

Degradable PEGylated protein conjugates utilizing RAFT polymerization

Decker

Maynard

2015

European Polymer Journal

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Poly(ethylene glycol) (PEG)-protein therapeutics exhibit enhanced pharmacokinetics, but have drawbacks including decreased protein activities and polymer accumulation in the body. Therefore a major aim for second-generation polymer therapeutics is to introduce degradability into the backbone. Herein we describe the synthesis of poly(poly(ethylene glycol methyl ether methacrylate)) (pPEGMA) degradable polymers with protein-reactive end-groups via reversible addition-fragmentation chain transfer (RAFT) polymerization, and the subsequent covalent attachment to lysozyme through a reducible disulfide linkage. RAFT copolymerization of cyclic ketene acetal (CKA) monomer 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) with PEGMA yielded two polymers with number-average molecular weight (Mn) (GPC) of 10.9 and 20.9 kDa and molecular weight dispersities (Ð) of 1.34 and 1.71, respectively. Hydrolytic degradation of the polymers was analyzed by 1H-NMR and GPC under basic and acidic conditions. The reversible covalent attachment of these polymers to lysozyme, as well as the hydrolytic and reductive cleavage of the polymer from the protein, was analyzed by gel electrophoresis and mass spectrometry. Following reductive cleavage of the polymer, an increase in activity was observed for both conjugates, with the released protein having full activity. This represents a method to prepare PEGylated proteins, where the polymer is readily cleaved from the protein and the main chain of the polymer is degradable.

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Section: Introductionmentioning

confidence: 99%

Degradable PEGylated protein conjugates utilizing RAFT polymerization

Decker

Maynard

2015

European Polymer Journal

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“…Those polymers include starch, chitosan, hyaluronic acid, cellulose, xanthan gum, gelatin, and so on. 42 Recently, we have reported a novel kind of injectable hydrogel which was synthesized using core-shell starch nanoparticles with aldehyde groups and poly(vinyl amine) (PVAM) with primary amines via a Schiff base reaction. 31 Chitosan is another biopolymer, which is a linear polysaccharide composed of randomly distributed b-(1-4)-linked D-glucosamine (deacetylated unit) and N-acetyl-Dglucosamine (acetylated unit).…”

Section: Introductionmentioning

confidence: 99%

In situ crosslinkable hydrogels formed from modified starch and O-carboxymethyl chitosan

Tan

et al. 2015

RSC Adv.

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An in situ hydrogel based on oxidation cholesterol starch (OCS) and O-carboxymethyl chitosan (CMCT) that is completely devoid of potentially cytotoxic small molecule cross-linkers and does not require complex manoeuvres or catalysis has been formulated and characterized. The network structure was created by Schiff base formation. The mechanical properties, internal morphology and swelling ability of the injectable hydrogel were examined. Rheological measurements demonstrated that increasing the concentration of the monomer improved the storage modulus. SEM showed that the hydrogel possessed a well-defined porous structure. In addition, the Schiff base reaction was acid sensitive. Under acid conditions, the hydrogel could hydrolyse quickly compared with high pH conditions. Doxorubicin (DOX) was used as a model drug to investigate the control and release properties of the hydrogel. The cytotoxic potential of the hydrogel was determined using an in vitro viability assay with L929 cells as a model and the results revealed that the hydrogel was non-cytotoxic.

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“…24 Both chain-ends were modified with polymerizable double bonds, i.e. [25][26][27][28][29][30][31][32][33][34][35][36][37][38] The formation of polyester during copolymerization depends upon the reaction conditions and comonomer type as CKAs can also undergo vinyl polymerization without isomerization leading to polyacetals with ring-retained structures. In addition, azide-alkyne coupling of diazide chain-end functionalised ABA triblock copolymers of PCL and PEO with tetrakis(2-propynyloxymethyl) methane (TMOP) was also applied.…”

Section: Introductionmentioning

confidence: 99%

Designed enzymatically degradable amphiphilic conetworks by radical ring-opening polymerization

2015

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A new route for the preparation of enzymatically degradable amphiphilic conetworks (APCNs) based on unsaturated polyesters by radical ring-opening copolymerization of vinylcyclopropane (VCP) with cyclic ketene acetal (CKA) is presented in this article. In the first step, the unsaturated biodegradable polyesters with random distribution of cross-linkable double bonds and degradable ester units were prepared by radical ring-opening copolymerization of VCP and CKA such as 2-methylene-4-phenyl-1,3-dioxolane (MPDO). Very similar reactivity ratios (r VCP = 0.23 ± 0.08 and r MPDO = 0.18 ± 0.02), unimodal gel permeation chromatography (GPC) curves and 2D NMR technique (heteronuclear multiple bond correlation, HMBC) showed the formation of random copolymers with unsaturation and ester units. The unsaturated units were used for cross-linking by radical polymerization with a hydrophilic macromonomer (oligo (ethylene glycol) methacrylate, OEGMA) in a second step for the formation of enzymatically degradable amphiphilic conetworks (APCNs). Enzymatic degradability was studied using Lipase from Pseudomonas cepacia. Due to the hydrophilic (HI) and hydrophobic (HO) microphase separation, the APCNs showed swelling in both water and organic solvents with different optical properties. The method provides an interesting route for making functional biodegradable APCNs using radical chemistry in the future by choosing appropriate vinyl comonomers. † Electronic supplementary information (ESI) available: Homopolymerization and characterization of VCP and reactivity ratio calculations. See

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Degradable and biocompatible aldehyde-functionalized glycopolymer conjugated with doxorubicin via acid-labile Schiff base linkage for pH-triggered drug release

Cited by 55 publications

References 40 publications

Degradable PEGylated protein conjugates utilizing RAFT polymerization

Degradable PEGylated protein conjugates utilizing RAFT polymerization

In situ crosslinkable hydrogels formed from modified starch and O-carboxymethyl chitosan

Designed enzymatically degradable amphiphilic conetworks by radical ring-opening polymerization

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