‘Living’ Controlled <i>in Situ</i> Gelling Systems: Thiol−Disulfide Exchange Method toward Tailor-Made Biodegradable Hydrogels

Wu, Decheng; Loh, Xian Jun; Wu, Yue; Lay, Chee Leng; Liu, Ye

doi:10.1021/ja106639c

Cited by 94 publications

(102 citation statements)

References 27 publications

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“…Fibroblasts, endothelial cells (HUVECs), and adult stem cells (pMSCs) were successfully encapsulated in situ and shown to proliferate over several days, even in the presence of unreacted thiols and the low-molecular-weight pyridine-2-thione cross-linking by-product. A similar although more complex approach was reported by Wu and co-workers, [ 162 ] who synthesized hyperbranched polymers consisting of a hydrophilic PEG shell and a hydrophobic core containing disulfi de linkages via a one-pot, two-step Michael reaction. During the Michael addition reaction, some free thiols remain unreacted, which can exchange with the disulfi des to form a hydrogel that remains stable for several months at physiological pH.…”

Section: Cross-linking Via Disulfi De Formationmentioning

confidence: 94%

“…[ 162,163 ] Choh and co-workers [ 163 ] demonstrated this approach by co-extruding HA pyridyl disulfi de (HA-PD) with PEGdithiol (PEG-DS) ( Figure 3 ), with simple mixing of these precursors at 37 °C in PBS resulting in gelation within 4-5 min. Of note, this exchange reaction facilitated gelation signifi cantly faster than the auto-oxidation of thiols.…”

Section: Cross-linking Via Disulfi De Formationmentioning

confidence: 99%

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Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

Patenaude

Smeets

Hoare

2014

Macromol. Rapid Commun.

165

125

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Hydrogels that can form spontaneously via covalent bond formation upon injection in vivo have recently attracted significant attention for their potential to address a variety of biomedical challenges. This review discusses the design rules for the effective engineering of such materials, and the major chemistries used to form injectable, in situ gelling hydrogels in the context of these design guidelines are outlined (with examples). Directions for future research in the area are addressed, noting the outstanding challenges associated with the use of this class of hydrogels in vivo.

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Section: Cross-linking Via Disulfi De Formationmentioning

confidence: 94%

Section: Cross-linking Via Disulfi De Formationmentioning

confidence: 99%

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

Patenaude

Smeets

Hoare

2014

Macromol. Rapid Commun.

165

125

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“…In the 1 H NMR spectra of DMAPA-Glyp and AEPZ-Glyp derivatives (Figure 2B), the proton resonance peaks at 1.0-3.2 ppm provided further confirmation that the oligoamine residues were conjugated with glycogen. 18,24 The DS values of the AEPZ-Glyp derivatives, however, were lower than those of the DMAPA-Glyp derivatives (Table 1), because of the steric hindrance between the AEPZ residues and the glucose units of glycogen.…”

Section: Synthesis Of Hyperbranched Cationic Glycogen Derivativesmentioning

confidence: 91%

An efficient nonviral gene-delivery vector based on hyperbranched cationic glycogen derivatives

Liu¹,

Ren²,

Liu³

et al. 2014

IJN

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Background The purpose of this study was to synthesize and evaluate hyperbranched cationic glycogen derivatives as an efficient nonviral gene-delivery vector. Methods A series of hyperbranched cationic glycogen derivatives conjugated with 3-(dimethylamino)-1-propylamine (DMAPA-Glyp) and 1-(2-aminoethyl) piperazine (AEPZ-Glyp) residues were synthesized and characterized by Fourier-transform infrared and hydrogen-1 nuclear magnetic resonance spectroscopy. Their buffer capacity was assessed by acid–base titration in aqueous NaCl solution. Plasmid deoxyribonucleic acid (pDNA) condensation ability and protection against DNase I degradation of the glycogen derivatives were assessed using agarose gel electrophoresis. The zeta potentials and particle sizes of the glycogen derivative/pDNA complexes were measured, and the images of the complexes were observed using atomic force microscopy. Blood compatibility and cytotoxicity were evaluated by hemolysis assay and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, respectively. pDNA transfection efficiency mediated by the cationic glycogen derivatives was evaluated by flow cytometry and fluorescence microscopy in the 293T (human embryonic kidney) and the CNE2 (human nasopharyngeal carcinoma) cell lines. In vivo delivery of pDNA in model animals (Sprague Dawley rats) was evaluated to identify the safety and transfection efficiency. Results The hyperbranched cationic glycogen derivatives conjugated with DMAPA and AEPZ residues were synthesized. They exhibited better blood compatibility and lower cytotoxicity when compared to branched polyethyleneimine (bPEI). They were able to bind and condense pDNA to form the complexes of 100–250 nm in size. The transfection efficiency of the DMAPA-Glyp/pDNA complexes was higher than those of the AEPZ-Glyp/pDNA complexes in both the 293T and CNE2 cells, and almost equal to those of bPEI. Furthermore, pDNA could be more safely delivered to the blood vessels in brain tissue of Sprague Dawley rats by the DMAPA-Glyp derivatives, and then expressed as green fluorescence protein, compared with the control group. Conclusion The hyperbranched cationic glycogen derivatives, especially the DMAPA-Glyp derivatives, showed high gene-transfection efficiency, good blood compatibility, and low cyto toxicity when transfected in vitro and in vivo, which are novel potential nonviral gene vectors.

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“…The formation of crosslink via the intermolecular disulfi de exchange reaction of poly(BAC2-AMPD1)-PEG is important to the fabrication and stability of the nanogels. There are several ways to facilitate the disulfi de exchange reaction such as adding catalytic amount of reducing agents such as dithiothreitol (DTT), [ 42,43 ] tuning to a basic pH [ 17,37 ] or applying heating. [ 41,44 ] In our work, the W/O emulsion was heated to 50 °C for various duration.…”

Section: Gsh -S-s--s-s--s-s--s-s--s-s--s-s--s-s--s-s--s-s--s-s--s-s--mentioning

confidence: 99%

“…[ 31 ] Poly(amido amine)s show low hemolytic activity and peptide-mimicking behaviors and have been explored for many biomedical applications such as drug delivery, [ 32,33 ] gene delivery, [ 34 ] fl uorescence imaging, [ 35 ] magnetic resonance imaging (MRI), [ 36 ] and preparation of hydrogels. [ 37 ] Here we report a surfactant-free emulsion-based preparation of nanogels from disulfi de-containing PEGylated hyperbranched poly(amido amine)s, poly(BAC2-AMPD1)-PEG. Poly(BAC2-AMPD1)-PEG was synthesized via Michael addition polymerization of 4-(aminomethyl)piperidine (AMPD) and double molar of N,N -cystaminebis(acrylamide) (BAC) followed by PEGylation (see Scheme S1 in the Supporting Information).…”

mentioning

confidence: 99%

Surfactant‐Free Emulsion‐Based Preparation of Redox‐Responsive Nanogels

Cheng

Wang

Kumar

et al. 2015

Macromol. Rapid Commun.

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A surfactant-free emulsion-based approach is developed for preparation of nanogels. A water-in-oil emulsion is generated feasibly from a mixture of water and a solution of disulfide-containing hyperbranched PEGylated poly(amido amine)s, poly(BAC2-AMPD1)-PEG, in chloroform. The water droplets in the emulsion are stabilized and filled with poly(BAC2-AMPD1)-PEG, and the crosslinked poly(amido amine)s nanogels are formed via the intermolecular disulfide exchange reaction. FITC-dextran is loaded within the nanogels by dissolving the compound in water before emulsification. Transmission electron microscopy and dynamic light scattering are applied to characterize the emulsion and the nanogels. The effects of the homogenization rate and the ratio of water/polymer are investigated. Redox-induced degradation and FITC-dextran release profile of the nanogels are monitored, and the results show efficient loading and redox-responsive release of FITC-dextran. This is a promising approach for the preparation of nanogels for drug delivery, especially for neutral charged carbohydrate-based drugs.

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‘Living’ Controlled in Situ Gelling Systems: Thiol−Disulfide Exchange Method toward Tailor-Made Biodegradable Hydrogels

Cited by 94 publications

References 27 publications

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

An efficient nonviral gene-delivery vector based on hyperbranched cationic glycogen derivatives

Surfactant‐Free Emulsion‐Based Preparation of Redox‐Responsive Nanogels

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