Drug Deliv. 2017 Nov;24(1):834-845. doi: 10.1080/10717544.2017.1326540. Preliminary study on fabrication, characterization and synergistic anti-lung cancer effects of self-assembled micelles of covalently conjugated celastrol-polyethylene glycol-ginsenoside Rh2 Abstract The aim of this study was to develop an amphipathic polyethylene glycol (PEG) derivative that was bi-terminally modified with celastrol and ginsenoside Rh2 (Celastrol-PEG-G Rh2). Such derivative was capable of forming novel, celastrol-loaded polymeric micelles (CG-M) for endo/lysosomal delivery and thereby synergistic treatment of lung cancer. Celastrol-PEG-G Rh2 with a yield of 55.6% was first synthesized and characterized. Its critical micellar concentration was 1 × 10-5 M, determined by pyrene entrapment method. CG-M had a small particle size of 121.53 ± 2.35 nm, a narrow polydispersity index of 0.214 ± 0.001 and a moderately negative zeta potential of -23.14 ± 3.15 mV. Celastrol and G Rh2 were rapidly released from CG-M under acidic and enzymatic conditions, but slowly released in normal physiological environments. In cellular studies, the internalization of celastrol and G Rh2 by human non-small cell lung cancer (A549) cells treated with CG-M was 5.8-fold and 1.8-fold higher than that of non-micelle control. Combinational therapy of celastrol and G Rh2 using CG-M exhibited synergistic anticancer activities in cell apoptosis and proliferation assays via rapid drug release within endo/lysosomes. Most importantly, the celastrol in CG-M exhibited a long elimination half-life of 445.3 ± 43.5 min and an improved area under the curve of 645060.8 ± 63640.7 ng/mL/h, that were 1.03-fold and 2.44-fold greater than those of non-micelle control, respectively. These findings suggest that CG-M is a promising vector for precisely releasing anticancer drugs within the tumor cells, and thereby exerts an improved synergistic anti-lung cancer effect. Keywords: Celastrol; anti-lung cancer; drug release; ginsenoside Rh2; micelle. Related products Abbreviation: pNP-PEG-pNP For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

POSS-modified PEG adhesives for wound closure October 2017 Chinese Journal of Polymer Science (English Edition) 35(10):1231-1242 DOI:10.1007/s10118-017-1958-x Abstract PEG-related adhesives are limited in clinical use because they are easy to swell and cannot support the cell growth. In this study, we produced a series of POSS-modified PEG adhesives with high adhesive strength. Introduction of inorganic hydrophobic POSS units decreased the swelling of the adhesives and enhanced cell adhesion and growth. The in vitro cytotoxicity and in vivo inflammatory response experiments clearly demonstrated that the adhesives were nontoxic and possessed excellent biocompatibility. Compared with the sutured wounds, the adhesive-treated wounds showed an accelerated healing process in wounded skin model of the Bama miniature pig, demonstrating that the POSS-modified PEG adhesive is a promising candidate for wound closure. Related products Abbreviation: 4-arm PEG-OH, 4-arm PEG-NH2 For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

One-pot synthesis of highly mechanical and redox-degradable polyurethane hydrogels based on tetra-PEG and disulfide/thiol chemistry Article information DOI https://doi.org/10.1039/C6RA04320H Abstract Highly mechanical hydrogels with stimuli degradability are promising scaffold materials for tissue engineering, due to their unique advantage of retaining mechanical strength in use, while being able to be readily removed by external stimuli after use.  However, it has always been a big challenge to integrate both good mechanical properties and stimuli degradability into one single hydrogel.  In this work, a series of tetra-PEG polyurethane hydrogels with tunable redox-degradability and a high compressive fracture strength has been synthesized by a one-pot method.  The good mechanical properties are owed to an extremely uniform network of tetra-PEG, and the redox-degradability is realized using cystamine, which contains a highly DTT-sensitive disulfide bond.  The mechanical strength of the as-prepared hydrogels reaches a megapascal range, and their complete degradation time can be flexibly adjusted from 4 to 22 days by controlling the proportion of cystamine.  With the above properties, these hydrogels are believed to have potential bio-applications. Related products Abbreviation: 4-arm PEG For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

J Mater Chem B. 2019 Apr 14;7(14):2330-2337.  doi: 10.1039/c8tb02928h.  Epub 2019 Mar 7. Microcapsule-embedded hydrogel patches for ultrasound responsive and enhanced transdermal delivery of diclofenac sodium Abstract Transdermal delivery of diclofenac sodium (DS) has drawn much attention for the advantages of avoiding first-pass metabolism, reduced systemic toxicity and better patient compliance, but the successful translation of reported transdermal drug delivery systems (TDDSs) is still limited by poor skin permeability and uncontrollable drug release.  Herein, we designed and fabricated a novel ultrasound responsive TDDS by embedding DS-loaded polyester microcapsules into a hydrogel patch based on four-armed poly(ethylene glycol).  The rational design endows the microcapsule-embedded hydrogel patch with good biocompatibility, excellent skin-adhesion properties and well-controlled ultrasound responsive release behavior.  More importantly, by employing ultrasound as a simultaneous trigger of drug release and efficient penetration enhancer, the encapsulated drug could be released and pass through the skin barrier rapidly under ultrasound, while without the action of ultrasound, a negligible amount of drug was released and penetrated into the subcutaneous tissues in ex vivo and in vivo transdermal drug release experiments, indicating that improved and controllable transdermal delivery of DS was achieved.  Our work demonstrated that the microcapsule-embedded hydrogel patch may be a promising candidate as an ultrasound responsive and enhanced TDDS of DS for treating diseases such as arthritis and topical soft tissue injuries. Related products Abbreviation: 4-arm-PEG-NHS, 4-arm-PEG-NH2 For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Maleimidophenyl isocyanates as postpolymerization modification agents and their applications in the synthesis of block copolymers Rikito Takashima, Jumpei Kida, Daisuke Aoki, Hideyuki Otsuka First published: 01 August 2019 https://doi.org/10.1002/pola.29450Citations: 8 ABSTRACT The maleimide structure is highly reactive, exemplified by thiol–ene click reactions with thiols and Diels–Alder reactions with furans.  Although postpolymerization modifications and macromolecular conjugations involving maleimide units have been widely studied, mostly due to their selectivity and high reactivity, little has been reported on the one-pot postpolymerization introduction of maleimides in polymer chains.  Herein, we report p-maleimidophenyl isocyanate and its derivatives as modification agents to introduce maleimide moieties by reaction with hydroxy groups into polymer chains.  The high reactivity of the resulting modification agents and of the corresponding maleimide structures once inserted in the polymer chains was examined by studying their reaction kinetics.  Furthermore, these modification agents were successfully applied to the synthesis of macromonomers for graft polymerization and various block copolymers, with, for example, AB-type, star-shaped, and H-shaped architectures. Related products Abbreviation: 4-arm PEG For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Soft Matter. 2016 Jan 21;12(3):798-805. doi: 10.1039/c5sm02015h. Epub 2015 Nov 4. Into the polymer brush regime through the "grafting-to" method: densely polymer-grafted rodlike viruses with an unusual nematic liquid crystal behavior Abstract The current work reports an intriguing discovery of how the force exerted on protein complexes like filamentous viruses by the strong interchain repulsion of polymer brushes can induce subtle changes of the constituent subunits at the molecular scale. Such changes transform into the macroscopic rearrangement of the chiral ordering of the rodlike virus in three dimensions. For this, a straightforward "grafting-to" PEGylation method has been developed to densely graft a filamentous virus with poly(ethylene glycol) (PEG). The grafting density is so high that PEG is in the polymer brush regime, resulting in straight and thick rodlike particles with a thin viral backbone. Scission of the densely PEGylated viruses into fragments was observed due to the steric repulsion of the PEG brush, as facilitated by adsorption onto a mica surface. The high grafting density of PEG endows the virus with an isotropic-nematic (I-N) liquid crystal (LC) phase transition that is independent of the ionic strength and the densely PEGylated viruses enter into the nematic LC phase at much lower virus concentrations. Most importantly, while the intact virus and the one grafted with PEG of low grafting density can form a chiral nematic LC phase, the densely PEGylated viruses only form a pure nematic LC phase. This can be traced back to the secondary to tertiary structural change of the major coat protein of the virus, driven by the steric repulsion of the PEG brush. Quantitative parameters characterising the conformation of the grafted PEG derived from the grafting density or the I-N LC transition are elegantly consistent with the theoretical prediction. Related products Abbreviation: mPEG-NHS For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Bioact Mater. 2017 May 6;3(1):48-54.  doi: 10.1016/j.bioactmat.2017.04.007.  eCollection 2018 Mar. Inhibition of HeLa cell growth by doxorubicin-loaded and tuftsin-conjugated arginate-PEG microparticles Abstract In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance, poly(ethylene glycol amine) (PEG)-modified alginate microparticles (ALG-PEG MPs) were developed then two different mechanisms were employed to load doxorubicin (Dox): 1) forming Dox/ALG-PEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG;  2) forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG, respectively.  Additionally, tuftsin (TFT), a natural immunomodulation peptide, was conjugated to MPs in order to enhance the efficiency of cellular uptake.  It was found that the Dox-ALG-PEG-TFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium, suggesting the role of covalent bonding in prolonging Dox retention.  Besides, the release of Dox from these MPs was pH-sensitive, and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4.  Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs, their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h, implying the effectiveness of TFT in enhancing cellular uptake of MPs.  Over a period of 48 h, Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant (p > 0.05).  In consideration of the prolonged and sustained release of Dox, Dox-ALG-PEG-TFT MPs possess the advantages for long-term treatment. Keywords: Cellular uptake;  Chemotherapy;  Controlled release;  Tuftsin. Related products Abbreviation: 4-arm-PEG For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Nat Commun.  2020 Mar 18;11(1):1435.   doi: 10.1038/s41467-020-14887-9. Fiber reinforced GelMA hydrogel to induce the regeneration of corneal stroma Bin Kong, Yun Chen, Rui Liu, Xi Liu, Changyong Liu, Zengwu Shao, Liming Xiong, Xianning Liu, Wei Sun, Shengli Mi Abstract Regeneration of corneal stroma has always been a challenge due to its sophisticated structure and keratocyte-fibroblast transformation.   In this study, we fabricate grid poly (ε-caprolactone)-poly (ethylene glycol) microfibrous scaffold and infuse the scaffold with gelatin methacrylate (GelMA) hydrogel to obtain a 3 D fiber hydrogel construct;   the fiber spacing is adjusted to fabricate optimal construct that simulates the stromal structure with properties most similar to the native cornea.   The topological structure (3 D fiber hydrogel, 3 D GelMA hydrogel, and 2 D culture dish) and chemical factors (serum, ascorbic acid, insulin, and β-FGF) are examined to study their effects on the differentiation of limbal stromal stem cells to keratocytes or fibroblasts and the phenotype maintenance, in vitro and in vivo tissue regeneration.   The results demonstrate that fiber hydrogel and serum-free media synergize to provide an optimal environment for the maintenance of keratocyte phenotype and the regeneration of damaged corneal stroma. Related products Abbreviation: 4-arm-PEG For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com