scholarly journals Selective Modification of Chitosan to Enable the Formation of Chitosan-DNA Condensates by Electron Donator Stabilization

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Karl E. Kador ◽  
Anuradha Subramanian

Chitosan, a polyaminosaccharide, has been investigated for its use in the field of drug-delivery and biomaterial applications because of its natural biocompatibility and polycationic properties. Chemical modifications of chitosan have been attempted in an effort to increase the transfection efficiency with respect to gene delivery applications; however, it is unknown how these modifications affect the formation of the condensates. This study attempts to determine the effects of modification of the cationic center of chitosan on the ability to condense DNA. Specifically, electron-donating or -withdrawing groups were used as modifiers of the cationic charge on the chitosan backbone to stabilize the protonated form of chitosan, which is necessary to form condensates and increase the efficiency of the polymer to condense DNA by yielding condensates at a lower nitrogen to phosphorous (N : P) ratio. While an N : P ratio of 7 is needed to condense DNA with unmodified chitosan, phthalate-modified chitosan yielded condensates were obtained at an N : P ratio of 1.0.

2010 ◽  
Vol 7 (6) ◽  
pp. 458-464
Author(s):  
Xiao-Li WU ◽  
Can ZHANG ◽  
Qi-Neng PING

2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 87
Author(s):  
Jaehong Park ◽  
Kyusik Kim ◽  
Sohee Jeong ◽  
Migyeom Lee ◽  
Tae-il Kim

In this work, highly osmotic oxidized sucrose-crosslinked polyethylenimine (SP2K) polymers were developed for gene delivery systems, and the transfection mechanism is examined. First, periodate-oxidized sucrose and polyethylenimine 2K (PEI2K) were crosslinked with various feed ratios via reductive amination. The synthesis was confirmed by 1H NMR and FTIR. The synthesized SP2K polymers could form positively charged (~40 mV zeta-potential) and nano-sized (150–200 nm) spherical polyplexes with plasmid DNA (pDNA). They showed lower cytotoxicity than PEI25K but concentration-dependent cytotoxicity. Among them, SP2K7 and SP2K10 showed higher transfection efficiency than PEI25K in both serum and serum-free conditions, revealing the good serum stability. It was found that SP2K polymers possessed high osmolality and endosome buffering capacity. The transfection experiments with cellular uptake inhibitors suggest that the transfection of SP2K polymers would progress by multiple pathways, including caveolae-mediated endocytosis. It was also thought that caveolae-mediated endocytosis of SP2K polyplexes would be facilitated through cyclooxygenase-2 (COX-2) expression induced by high osmotic pressure of SP2K polymers. Confocal microscopy results also supported that SP2K polyplexes would be internalized into cells via multiple pathways and escape endosomes efficiently via high osmolality and endosome buffering capacity. These results demonstrate the potential of SP2K polymers for gene delivery systems.


2021 ◽  
Vol 22 (4) ◽  
pp. 1776
Author(s):  
Elham Pishavar ◽  
Hongrong Luo ◽  
Johanna Bolander ◽  
Antony Atala ◽  
Seeram Ramakrishna

Progenitor cells derived from the retinal pigment epithelium (RPECs) have shown promise as therapeutic approaches to degenerative retinal disorders including diabetic retinopathy, age-related macular degeneration and Stargardt disease. However, the degeneration of Bruch’s membrane (BM), the natural substrate for the RPE, has been identified as one of the major limitations for utilizing RPECs. This degeneration leads to decreased support, survival and integration of the transplanted RPECs. It has been proposed that the generation of organized structures of nanofibers, in an attempt to mimic the natural retinal extracellular matrix (ECM) and its unique characteristics, could be utilized to overcome these limitations. Furthermore, nanoparticles could be incorporated to provide a platform for improved drug delivery and sustained release of molecules over several months to years. In addition, the incorporation of tissue-specific genes and stem cells into the nanostructures increased the stability and enhanced transfection efficiency of gene/drug to the posterior segment of the eye. This review discusses available drug delivery systems and combination therapies together with challenges associated with each approach. As the last step, we discuss the application of nanofibrous scaffolds for the implantation of RPE progenitor cells with the aim to enhance cell adhesion and support a functionally polarized RPE monolayer.


Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 437
Author(s):  
Milena Álvarez-Viñas ◽  
Sandra Souto ◽  
Noelia Flórez-Fernández ◽  
Maria Dolores Torres ◽  
Isabel Bandín ◽  
...  

Carrageenan and carrageenan oligosaccharides are red seaweed sulfated carbohydrates with well-known antiviral properties, mainly through the blocking of the viral attachment stage. They also exhibit other interesting biological properties and can be used to prepare different drug delivery systems for controlled administration. The most active forms are λ-, ι-, and κ-carrageenans, the degree and sulfation position being determined in their properties. They can be obtained from sustainable worldwide available resources and the influence of manufacturing on composition, structure, and antiviral properties should be considered. This review presents a survey of the antiviral properties of carrageenan in relation to the processing conditions, particularly those assisted by intensification technologies during the extraction stage, and discusses the possibility of further chemical modifications.


2021 ◽  
Vol 32 (5) ◽  
pp. 1924-1950
Author(s):  
Amir Ghaderpour ◽  
Zohreh Hoseinkhani ◽  
Reza Yarani ◽  
Sina Mohammadiani ◽  
Farshid Amiri ◽  
...  

2021 ◽  
Vol 184 ◽  
pp. 218-234
Author(s):  
Paulo Vitor França Lemos ◽  
Henrique Rodrigues Marcelino ◽  
Lucas Guimarães Cardoso ◽  
Carolina Oliveira de Souza ◽  
Janice Izabel Druzian

Author(s):  
Yana V. Tarakanchikova ◽  
Dmitrii S. Linnik ◽  
Tatiana Mashel ◽  
Albert R. Muslimov ◽  
Sergey Pavlov ◽  
...  

Polymers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 133
Author(s):  
Yu-Che Cheng ◽  
Shu-Lin Guo ◽  
Kun-Da Chung ◽  
Wei-Wen Hu

To sustain gene delivery and elongate transgene expression, plasmid DNA and cationic nonviral vectors can be deposited through layer-by-layer (LbL) assembly to form polyelectrolyte multilayers (PEMs). Although these macromolecules can be released for transfection purposes, their entanglement only allows partial delivery. Therefore, how to efficiently deliver immobilized genes from PEMs remains a challenge. In this study, we attempt to facilitate their delivery through the pretreatment of the external electrical field. Multilayers of polyethylenimine (PEI) and DNA were deposited onto conductive polypyrrole (PPy), which were placed in an aqueous environment to examine their release after electric field pretreatment. Only the electric field perpendicular to the substrate with constant voltage efficiently promoted the release of PEI and DNA from PEMs, and the higher potential resulted in the more releases which were enhanced with treatment time. The roughness of PEMs also increased after electric field treatment because the electrical field not only caused electrophoresis of polyelectrolytes and but also allowed electrochemical reaction on the PPy electrode. Finally, the released DNA and PEI were used for transfection. Polyplexes were successfully formed after electric field treatment, and the transfection efficiency was also improved, suggesting that this electric field pretreatment effectively assists gene delivery from PEMs and should be beneficial to regenerative medicine application.


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