scholarly journals Chondroitin Sulfate Capsule System for Efficient and Secure Gene Delivery

2010 ◽  
Vol 13 (3) ◽  
pp. 351 ◽  
Author(s):  
Tomoaki Kurosaki ◽  
Takashi Kitahara ◽  
Shintaro Fumoto ◽  
Koyo Nishida ◽  
Kayo Yamamoto ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Chondroitin Sulfate ◽  
Transfection Efficiency ◽  
Animal Experiments ◽  
Ternary Complexes ◽  
Trimethylammonium Chloride ◽  
Cationic Polymers ◽  
Low Cytotoxicity

Purpose. In this study, we developed various ternary complexes of encapsulated polyplexes and lipoplexes using chondroitin sulfate (CS) and investigated their universal usefulness for gene delivery. Methods. To prepare the cationic complexes, pDNA was mixed with some cationic vectors such as poly-L-arginine, poly-L-lysine, N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethylammonium chloride (DOTMA)-cholesterol liposomes, and DOTMA- dioleylphosphatidylethanolamine (DOPE) liposomes. CS was added to the cationic complexes for constructions of ternary complexes. We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of the ternary complexes. Result. The cationic polymers and cationic liposomes bound to pDNA and formed stable cationic polyplexes and lipoplexes, respectively. Those cationic complexes showed high transgene efficiency in B16-F10 cells; however, they also had high cytotoxicity and strong agglutination with erythrocytes. CS could encapsulate the polyplexes and lipoplexes and form stable anionic particles without disrupting their structures. The ternary complexes encapsulated by CS showed high transgene efficiency in B16-F10 cells with low cytotoxicity and agglutination. As the result of animal experiments, the polyplexes had little transgene efficiency after intravenous administration in mice, whereas polyplexes encapsulated by CS showed specifically high transgene efficiency in the spleen. The capsulation of CS, however, reduced the high transgene efficiency of the lipoplexes. Conclusion. These results indicate that CS can contribute to polyplex-mediated gene delivery systems for effective and safe gene therapy.

scholarly journals A Valid Bisphosphonate Modified Calcium Phosphate-Based Gene Delivery System: Increased Stability and Enhanced Transfection Efficiency In Vitro and In Vivo

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 468 ◽  
Author(s):  
Zhao ◽  
Li ◽  
Chen ◽  
Hu
Keyword(s):  
Calcium Phosphate ◽  
Gene Delivery ◽  
Tissue Specificity ◽  
Transfection Efficiency ◽  
Hybrid Nanoparticles ◽  
In Vivo Studies ◽  
Adsorptive Capacity ◽  
Low Cytotoxicity

Calcium phosphate (CaP) nanoparticles, as a promising vehicle for gene delivery, have been widely used owing to their biocompatibility, biodegradability and adsorptive capacity for nucleic acids. Unfortunately, their utility in vivo has been profoundly restricted due to numerous technical barriers such as the lack of tissue specificity and limited transfection efficiency, as well as uncontrollable aggregation over time. To address these issues, an effective conjugate folate-polyethylene glycol-pamidronate (shortened as FA-PEG-Pam) was designed and coated on the surface of CaP/NLS/pDNA (CaP/NDs), forming a versatile gene carrier FA-PEG-Pam/CaP/NDs. Inclusion of FA-PEG-Pam significantly reduced the size of CaP nanoparticles, thus inhibiting the aggregation of CaP nanoparticles. FA-PEG-Pam/CaP/NDs showed better cellular uptake than mPEG-Pam/CaP/NDs, which could be attributed to the high-affinity interactions between FA and highly expressed FR. Meanwhile, FA-PEG-Pam/CaP/NDs had low cytotoxicity and desired effect on inducing apoptosis (71.1%). Furthermore, FA-PEG-Pam/CaP/NDs showed admirable transfection efficiency (63.5%) due to the presence of NLS peptides. What’s more, in vivo studies revealed that the hybrid nanoparticles had supreme antitumor activity (IR% = 58.7%) among the whole preparations. Altogether, FA-PEG-Pam/CaP/NDs was expected to be a hopeful strategy for gene delivery.

Guanidine-rich helical polypeptides bearing hydrophobic amino acid pendants for efficient gene delivery

2021 ◽  
Author(s):  
Zikun Yu ◽  
Zhimin Zhang ◽  
Jing Yan ◽  
Ziyin Zhao ◽  
Chenglong Ge ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Amino Acid ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
Hydrophobic Amino Acid ◽  
High Transfection Efficiency ◽  
Efficient Gene ◽  
Low Cytotoxicity

Guanidine-rich helical polypeptides bearing hydrophobic amino acid pendants displayed high transfection efficiency both in vitro and in vivo and low cytotoxicity toward applications in gene therapy.

Evaluation of low molecular weight polyethylenimine-introduced chitosan for gene delivery to mesenchymal stem cells

2020 ◽  
Vol 10 (7) ◽  
pp. 1170-1176
Author(s):  
Minchen Liu ◽  
Yulan Hu ◽  
Yi Feng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
A549 Cells ◽  
Safety Evaluation ◽  
Physicochemical Characteristics ◽  
Hatching Rate

This study aimed to examine the transfection ability of polyethylenimine (PEI) (1800 Da)-grafted chitosan (10 kDa) (CP), a newly synthesized PEI derivative, in mesenchymal stem cells (MSCs). The safety evaluation of the complex/DNA was studied in vitro and in vivo. In addition, CP/pGL3 was applied to investigate the effects of transfection efficiency. In this study, CP/DNA can be formed with compatible physicochemical characteristics for gene delivery. CP cytotoxicity decreased in A549 cells. Moreover, a zebrafish embryo model was used for evaluating the safety in vivo. Compared to the PEI (25 kDa) group, the zebrafish hatching rate increased and the mortality rate decreased in the CP/DNA group, which provided an indication of the safety of CP. In comparison with chitosan (100 kDa)-PEI (1200 Da), CP's transfection efficiency was higher in both A549 cells and MSCs. This study aimed to lay the foundation for further applications of CP in gene delivery. Therefore, further gene therapy investigations of CP by using MSCs need to be performed.

Receptor-Mediated Gene Delivery Using Chitosan Derivatives In Vitro and In Vivo

2007 ◽  
Vol 342-343 ◽  
pp. 449-452 ◽  
Author(s):  
Tae Hee Kim ◽  
Hua Jin ◽  
Hyun Woo Kim ◽  
Myung Haing Cho ◽  
Jae Woon Nah ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Gene Delivery System ◽  
Targeted Gene Delivery ◽  
Cell Specificity ◽  
Selective Delivery

The key strategy for the advancement of gene therapy is the development of an efficient targeted gene delivery system into cells. The targeted gene delivery system is especially important in non-viral gene transfer which shows the relatively low transfection efficiency. It also opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been considered to be a good candidate for gene delivery system, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In this study, we focused on the chemical modification of chitosan for enhancement of cell specificity and transfection efficiency. Also, the potential of clinical application was investigated.

scholarly journals Exploitation of De Novo Helper-Lipids for Effective Gene Delivery.

2009 ◽  
Vol 11 (4) ◽  
pp. 56 ◽  
Author(s):  
Tomoaki Kurosaki ◽  
Takashi Kitahara ◽  
Mugen Teshima ◽  
Koyo Nishida ◽  
Junzo Nakamura ◽  
...  
Keyword(s):  
Gene Delivery ◽  
De Novo ◽  
Transfection Efficiency ◽  
The Other ◽  
Penetration Enhancers ◽  
Cell Toxicity ◽  
In Vivo Transfection ◽  
In Vitro Transfection

Purpose: In gene delivery, a fusogenic lipid such as dioleyl phosphatidylethanolamine (DOPE) which is a component of cationic liposomal vector is important factor for effective transfection efficiency. We investigated the effect of penetration enhancers as alternative helper-lipids to DOPE. Methods: Transdermal penetraion enhancers such as N-lauroylsarcosine (LS), (R)-(+)-limonene (LM), vitamin E (VE), and phosphatidyl choline from eggs (EggPC) were used in this experiments as helper-lipids with N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethlylammonium chloride (DOTMA) and cholesterol (CHOL). We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of plasmid DNA/cationic liposomes complexes. Results: In transfection experiments in vitro, the cationic lipoplexes containing LS had highest transfection efficiency among the other lipoplexes independently of FBS. Furthermore, the lipoplexes containing LS had lowest cell toxicity among the other lipoplexes in the presence of FBS. As the results of erythrocytes interaction experiment, DOTMA/LS/CHOL, DOTMA/VE/CHOL, and DOTMA/EggPC/CHOL lipoplexes showed extremely lower hematotoxicity. On the basis of these results, the in vivo transfection efficiencies of the lipoplexes were examined. The lipoplexes containing LS had the highest transfection activity among the other lipoplexes. Conclusion: In conclusion, several transdermal penetration enhancers are available for alternative helper-lipids to DOPE in cationic liposomal vectors. Among them, DOTMA/LS/CHOL lipoplexes showed superior characteristics in in vitro transfection efficiency, cell toxicity, hematotoxicity, and in vivo transfection efficiency.

Defined pH-sensitive nanogels as gene delivery platform for siRNA mediated in vitro gene silencing

2017 ◽  
Vol 5 (11) ◽  
pp. 2328-2336 ◽  
Author(s):  
Mathias Dimde ◽  
Falko Neumann ◽  
Felix Reisbeck ◽  
Svenja Ehrmann ◽  
Jose Luis Cuellar-Camacho ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Gene Silencing ◽  
Transfection Efficiency ◽  
Genetic Material ◽  
Ph Sensitive ◽  
Carrier System ◽  
High Transfection Efficiency ◽  
Delivery Platform ◽  
Low Cytotoxicity

An advanced cationic carrier system which combines high transfection efficiency with low cytotoxicity and a control over the release of the encapsulated genetic material by the reduction of the multivalent architecture upon pH triggered degradation was developed.

Tunable PEGylation of branch-type PEI/DNA polyplexes with a compromise of low cytotoxicity and high transgene expression: in vitro and in vivo gene delivery

2017 ◽  
Vol 5 (24) ◽  
pp. 4732-4744 ◽  
Author(s):  
A. Venault ◽  
Y.-C. Huang ◽  
J. W. Lo ◽  
C.-J. Chou ◽  
A. Chinnathambi ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transgene Expression ◽  
In Vivo Gene Delivery ◽  
Low Cytotoxicity ◽  
Branch Type ◽  
Delivery Efficiency

Although PEGylated polyplexes for gene delivery are widespread, there is a need for an in-depth investigation of the role of the PEGylation degree on the delivery efficiency of the systems.

scholarly journals Investigation of DNA Spectral Conformational Changes and Polymer Buffering Capacity in Relation to Transfection Efficiency of DNA/Polymer Complexes

2009 ◽  
Vol 12 (3) ◽  
pp. 346 ◽  
Author(s):  
Jong Yuh Cherng
Keyword(s):  
Conformational Changes ◽  
Transfection Efficiency ◽  
Dna Interaction ◽  
Buffering Capacity ◽  
Cationic Polymers ◽  
Polymer Complexes ◽  
Before And After ◽  
Stretching Vibration

Purpose. The relation between transfection efficiency of DNA/polymer complexes and DNA conformational alterations is investigated. The buffering capacity of several synthetic polymers is also studied to relate their performance in transfection efficiency. Methods. The cationic polymer/DNA interaction was evaluated by measuring the alteration of DNA secondary structures in solution before and after the addition of polymer with ATR-FTIR technique. The degree of protonation in aqueous cationic polymers is varied upon pH and different structures. A polymer capable of protonation acts like a proton sponge to react with H+ in titration with HCl. This characteristic was evaluated in relation to transfection efficiency because the capacity would help the release of endocytotic DNA from endosome/lysosome on its way to expression. Results. IR results show that the antisymmetric PO2- vibration of DNA (at 1224 cm-1) shifts toward lower frequencies in complexation with PEI or PLLys (these polymers are able to transfect DNA). By contrast, the antisymmetric PO2- vibration of DNA in presence of PDAMA or dextran (these polymers are poor in DNA transfection) shows a shifting to higher frequencies or no alteration was observed. Interestingly, the polymers with best performance in transfection efficiency are in this order: PEI>PDMAEMA>PLLys>PDAMA>dextran which is in the same order as their polymer buffering capacity. These facts indicate polymers possessing better buffering capacity could result in higher transfection efficiency. Also, we have demonstrated in this paper that the antisymmetric PO2- stretching vibration in IR spectra is sensitive while binding of cationic polymers to DNA. These findings are useful for the development of polymer-based gene delivery systems with better performance in vitro and in vivo

scholarly journals Interaction kinetics of peptide lipids-mediated gene delivery

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yinan Zhao ◽  
Tianyi Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. Results As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (− 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid. Conclusions The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

Sign in / Sign up

Export Citation Format

Share Document