scholarly journals PEGylated Amine-Functionalized Poly(ε-caprolactone) for the Delivery of Plasmid DNA

Materials ◽  
2020 ◽  
Vol 13 (4) ◽  
pp. 898 ◽  
Author(s):  
Amin Jafari ◽  
Nika Rajabian ◽  
Guojian Zhang ◽  
Mohamed Alaa Mohamed ◽  
Pedro Lei ◽  
...  

As a promising strategy for the treatment of various diseases, gene therapy has attracted increasing attention over the past decade. Among various gene delivery approaches, non-viral vectors made of synthetic biomaterials have shown significant potential. Due to their synthetic nature, non-viral vectors can have tunable structures and properties by using various building units. In particular, they can offer advantages over viral vectors with respect to biosafety and cytotoxicity. In this study, a well-defined poly(ethylene glycol)-block-poly(α-(propylthio-N,N-diethylethanamine hydrochloride)-ε-caprolactone) diblock polymer (PEG-b-CPCL) with one poly(ethylene glycol) (PEG) block and one tertiary amine-functionalized cationic poly(ε-caprolactone) (CPCL) block, as a novel non-viral vector in the delivery of plasmid DNA (pDNA), was synthesized and studied. Despite having a degradable polymeric structure, the polymer showed remarkable hydrolytic stability over multiple weeks. The optimal ratio of the polymer to pDNA for nanocomplex formation, pDNA release from the nanocomplex with the presence of heparin, and serum stability of the nanocomplex were probed through gel electrophoresis. Nanostructure of the nanocomplexes was characterized by DLS and TEM imaging. Relative to CPCL homopolymers, PEG-b-CPCL led to better solubility over a wide range of pH. Overall, this work demonstrates that PEG-b-CPCL possesses a range of valuable properties as a promising synthetic vector for pDNA delivery.

2018 ◽  
Vol 47 (3) ◽  
pp. 426-432 ◽  
Author(s):  
Sivan Yogev ◽  
Ayelet Shabtay-Orbach ◽  
Abraham Nyska ◽  
Boaz Mizrahi

Thermoresponsive materials have the ability to respond to a small change in temperature—a property that makes them useful in a wide range of applications and medical devices. Although very promising, there is only little conclusive data about the cytotoxicity and tissue toxicity of these materials. This work studied the biocompatibility of three Food and Drug Administration approved thermoresponsive polymers: poly( N-isopropyl acrylamide), poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) tri-block copolymer, and poly(lactic acid-co-glycolic acid) and poly(ethylene glycol) tri-block copolymer. Fibroblast NIH 3T3 and HaCaT keratinocyte cells were used for the cytotoxicity testing and a mouse model for the in vivo evaluation. In vivo results generally showed similar trends as the results seen in vitro, with all tested materials presenting a satisfactory biocompatibility in vivo. pNIPAM, however, showed the highest toxicity both in vitro and in vivo, which was explained by the release of harmful monomers and impurities. More data focusing on the biocompatibility of novel thermoresponsive biomaterials will facilitate the use of existing and future medical devices.


2014 ◽  
Vol 15 (3) ◽  
pp. 997-1001 ◽  
Author(s):  
Shoichiro Asayama ◽  
Atsushi Nohara ◽  
Yoichi Negishi ◽  
Hiroyoshi Kawakami

2007 ◽  
Vol 342-343 ◽  
pp. 425-428 ◽  
Author(s):  
Dhananjay Jere ◽  
Tae Hee Kim ◽  
Rohidas B. Arote ◽  
Hu Lin Jiang ◽  
Myung Haing Cho ◽  
...  

Vectors are vital aspect of gene delivery system which decides the success of gene therapy. Efficient transfection with minimum or no toxicity, are two principal aims of any gene delivery system. In this our study, we rationally developed biodegradable water soluble poly(ßamino ester) (PAE) based on spermine (SPR) and poly (ethylene glycol) (PEG), by Michael-type addition reaction and further studied for its potential as a gene carrier. Confirmation of synthesized PAE was done by proton NMR spectroscopy. In gel retardation assay, the PAEs have shown good DNA binding ability over wide range of polyplexes. The addition of PEG over SPR resulted in a novel PAE with higher degree of safety and transfection efficiency as compared with polyethylenimine 25K (PEI) when studied in 293T human kidney carcinoma cells.


2012 ◽  
Vol 1233 ◽  
pp. 30-35 ◽  
Author(s):  
Hans-Olof Johansson ◽  
Tiago Matos ◽  
Juliana S. Luz ◽  
Eloi Feitosa ◽  
Carla C. Oliveira ◽  
...  

2017 ◽  
Vol 13 ◽  
pp. 1963-1968 ◽  
Author(s):  
Michael Y Malca ◽  
Pierre-Olivier Ferko ◽  
Tomislav Friščić ◽  
Audrey Moores

Poly(ethylene glycol) (PEG) is a linear polymer with a wide range of applications in chemical manufacturing, drug development and nanotechnology. PEG derivatives are being increasingly used to covalently modify small molecule and peptide drugs, as well as bioactive nanomaterials in order to improve solubility in biological serum, reduce immunogenicity, and enhance pharmacokinetic profiles. Herein we present the development of mechanochemical procedures for PEG functionalization without the need for bulk solvents, offering a cleaner and more sustainable alternative to existing solution-based PEG procedures. The herein presented mechanochemical procedures enable rapid and solvent-free derivatization of PEG with tosyl, bromide, thiol, carboxylic acid or amine functionalities in good to quantitative yields and with no polymer chain oligomerization, proving the versatility of the method.


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