scholarly journals Transdermal Delivery of Small Interfering RNA with Elastic Cationic Liposomes in Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yoshiyuki Hattori ◽  
Masataka Date ◽  
Shohei Arai ◽  
Kumi Kawano ◽  
Etsuo Yonemochi ◽  
...  
Keyword(s):  
Sirna Delivery ◽  
Cationic Lipid ◽  
Tween 80 ◽  
Sodium Cholate ◽  
Cationic Liposomes ◽  
Gene Suppression ◽  
Liposomal Formulations ◽  
Siha Cells ◽  
Interfering Rna ◽  
Edge Activator

We developed elastic cationic liposomal vectors for transdermal siRNA delivery. These liposomes were prepared with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid and sodium cholate (NaChol) or Tween 80 as an edge activator. When NaChol or Tween 80 was included at 5, 10, and 15% (w/w) into DOTAP liposomal formulations (C5-, C10-, and C15-liposomes and T5-, T10-, and T15-liposomes), C15- and T10-liposomes showed 2.4- and 2.7-fold-higher elasticities than DOTAP liposome, respectively. Although the sizes of all elastic liposomes prepared in this study were about 80–90 nm, the sizes of C5-, C10- and C15-liposome/siRNA complexes (lipoplexes) were about 1,700–1,800 nm, and those of T5-, T10-, and T15-lipoplexes were about 550–780 nm. Their elastic lipoplexes showed strong gene suppression by siRNA without cytotoxicity when transfected into human cervical carcinoma SiHa cells. Following skin application of the fluorescence-labeled lipoplexes in mice, among the elastic lipoplexes, C15- and T5-lipoplexes showed effective penetration of siRNA into skin, compared with DOTAP lipoplex and free siRNA solution. These data suggest that elastic cationic liposomes containing an appropriate amount of NaChol or Tween 80 as an edge activator could deliver siRNA transdermally.

Systematic Evaluation of Protein-Based Nanoparticles for Stable Delivery of Small Interfering RNA

2020 ◽  
Vol 16 (7) ◽  
pp. 1169-1181
Author(s):  
Dhananjay Suresh ◽  
Brian Jenkins ◽  
Ajit Zambre ◽  
Anandhi Upendran ◽  
Raghuraman Kannan
Keyword(s):  
High Stability ◽  
Sirna Delivery ◽  
Systematic Investigation ◽  
Systematic Evaluation ◽  
Cellular Delivery ◽  
Gelatin Nanoparticles ◽  
Gene Suppression ◽  
Protein Levels ◽  
Delivery Vehicles ◽  
Interfering Rna

Developing a delivery vehicle to protect siRNA from degradation is a significant challenge. To solve this challenge, researchers attempted to use protein-based nanoparticles to deliver siRNA with limited to moderate success. However, a systematic investigation of comparing the ability of different protein-based nanoparticles as vehicles to deliver siRNA stably within cells is still unavailable. Therefore, in this study we synthesized a library of both non-targeted (proteinsiRNA) nanoparticles (NPs) and targeted (antibody conjugated protein-siRNA) NPs and evaluated ability to stably deliver siRNA in to cells to silence the gene of interest. We investigated nanoparticles of casein, bovine serum albumin, and gelatin for the delivery of siRNA. We synthesized and characterized a total of 12 nanoconjugates; in these conjugates, we either encapsulated, electrostatically attached, or covalently conjugated siRNA. We evaluated the efficiency of attaching siRNA to nanoconjugates, stability, and cellular delivery. The ability of siRNA to silence the protein of interest in cancer cells was also investigated. Among non-targeted conjugates, BSA matrix imparted relatively high stability to siRNA when encapsulated. Among targeted nanoconjugates, gelatin nanoparticles rendered high stability to siRNA upon covalent conjugation to the surface. On comparing with both targeted and non-targeted NPs for release of siRNA within cells, antibody-gelatin-siRNA conjugate exhibited high release and functional activity (down-regulation of target protein levels) within the cells as confirmed by both fluorescence imaging and Western blotting. In summary, our investigations show that targeted gelatin nanoparticles and non-targeted BSA nanoparticles possess high stability and excellent gene suppression capabilities and warrants further studies. We can extend the results from this study to develop stable siRNA delivery vehicles to specifically silence the protein of interest.

The development of tertiary amine cationic lipids for safe and efficient siRNA delivery

2019 ◽  
Vol 7 (7) ◽  
pp. 2777-2792 ◽  
Author(s):  
Ziming Lin ◽  
Moxyel Bao ◽  
Zexuan Yu ◽  
Lingjing Xue ◽  
Caoyun Ju ◽  
...  
Keyword(s):  
Tertiary Amine ◽  
Sirna Delivery ◽  
Cationic Lipid ◽  
Cationic Liposomes ◽  
Cationic Lipids

Tertiary amine-derived cationic lipid serves as the primary lipid of cationic liposomes, which can balance the effectiveness and safety of siRNA vectors.

scholarly journals Influence of the Flexible Liposomes on the Skin Deposition of a Hydrophilic Model Drug, Carboxyfluorescein: Dependency on Their Composition

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Mohamed Badran ◽  
Khaled Shalaby ◽  
Abdullah Al-Omrani
Keyword(s):  
Zeta Potential ◽  
Entrapment Efficiency ◽  
Tween 80 ◽  
Sodium Cholate ◽  
Hydrophilic Drugs ◽  
Liposomal Formulations ◽  
Skin Deposition ◽  
Drug Entrapment Efficiency ◽  
Model Drug

This study focuses on the effect of different flexible liposomes containing sodium cholate, Tween 80, or cineol on skin deposition of carboxyfluorescein (CF). Size distribution, morphology, zeta potential, and stability of the prepared vesicles were evaluated. The influence of these systems on the skin deposition of CF utilizing rat skin as membrane model was investigated. Results showed that all of the investigated liposomes had almost spherical shapes with low polydispersity (PDI < 0.3) and particles size range from 83 to 175 nm. All liposomal formulations exhibited negative zeta potential, good drug entrapment efficiency, and stability.In vitroskin deposition data showed that flexible liposomes gave significant deposition of CF on the skin compared to conventional liposomes and drug solutions. This study revealed that flexible liposomes, containing cineole, were able to deliver higher amount of CF suggesting that the hydrophilic drugs delivery to the skin was strictly correlated to the vesicle composition.

scholarly journals Anti-c-myc cholesterol based lipoplexes as onco-nanotherapeutic agents in vitro

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 770
Author(s):  
Saffiya Habib ◽  
Aliscia Daniels ◽  
Mario Ariatti ◽  
Moganavelli Singh
Keyword(s):  
Sirna Delivery ◽  
Cationic Lipid ◽  
Lipid Vesicles ◽  
Breast Adenocarcinoma ◽  
Protein Levels ◽  
Anti Cancer ◽  
Attractive Option ◽  
Interfering Rna ◽  
Mcf 7

Background: Strategies aimed at inhibiting the expression of the c-myc oncogene could provide the basis for alternative cancer treatment. In this regard, silencing c-myc expression using small interfering RNA (siRNA) is an attractive option. However, the development of a clinically viable, siRNA-based, c-myc silencing system is largely dependent upon the design of an appropriate siRNA carrier that can be easily prepared. Nanostructures formed by the electrostatic association of siRNA and cationic lipid vesicles represent uncomplicated siRNA delivery systems. Methods: This study has focused on cationic liposomes prepared with equimolar quantities of the cytofectin, N,N-dimethylaminopropylamido-succinylcholesteryl-formylhydrazide (MS09), and cholesterol (Chol) for the development of a simple, but effective anti- c-myc onco-nanotherapeutic agent. Liposomes formulated with dioleoylphosphatidylethanolamine (DOPE) in place of Chol as the co-lipid were included for comparative purposes. Results: Liposomes successfully bound siRNA forming lipoplexes of less than 150 nm in size, which assumed bilamellar aggregrates. The liposome formulations were well tolerated in the human breast adenocarcinoma (MCF-7) and colon carcinoma (HT-29) cells, which overexpress c-myc. Lipoplexes directed against the c-myc transcript mediated a dramatic reduction in c-myc mRNA and protein levels. Moreover, oncogene knockdown and anti-cancer effects were superior to that of Lipofectamine™ 3000. Conclusion: This anti- c-myc MS09:Chol lipoplex exemplifies a simple anticancer agent with enhanced c-myc gene silencing potential in vitro

Effect of cationic lipid in cationic liposomes on siRNA delivery into the lung by intravenous injection of cationic lipoplex

2018 ◽  
Vol 27 (2) ◽  
pp. 217-227 ◽  
Author(s):  
Yoshiyuki Hattori ◽  
Mari Nakamura ◽  
Nozomi Takeuchi ◽  
Kyoko Tamaki ◽  
Satono Shimizu ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Sirna Delivery ◽  
Cationic Lipid ◽  
Cationic Liposomes

scholarly journals Anti-c-myc cholesterol based lipoplexes as onco-nanotherapeutic agents in vitro

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 770 ◽  
Author(s):  
Saffiya Habib ◽  
Aliscia Daniels ◽  
Mario Ariatti ◽  
Moganavelli Singh
Keyword(s):  
Sirna Delivery ◽  
Cationic Lipid ◽  
Lipid Vesicles ◽  
Breast Adenocarcinoma ◽  
Protein Levels ◽  
Anti Cancer ◽  
Attractive Option ◽  
Interfering Rna ◽  
Mcf 7

Background: Strategies aimed at inhibiting the expression of the c-myc oncogene could provide the basis for alternative cancer treatment. In this regard, silencing c-myc expression using small interfering RNA (siRNA) is an attractive option. However, the development of a clinically viable, siRNA-based, c-myc silencing system is largely dependent upon the design of an appropriate siRNA carrier that can be easily prepared. Nanostructures formed by the electrostatic association of siRNA and cationic lipid vesicles represent uncomplicated siRNA delivery systems. Methods: This study has focused on cationic liposomes prepared with equimolar quantities of the cytofectin, N,N-dimethylaminopropylamido-succinylcholesteryl-formylhydrazide (MS09), and cholesterol (Chol) for the development of a simple, but effective anti-c-myc onco-nanotherapeutic agent. Liposomes formulated with dioleoylphosphatidylethanolamine (DOPE) in place of Chol as the co-lipid were included for comparative purposes. Results: Liposomes successfully bound siRNA forming lipoplexes of less than 200 nm in size, which assumed globular, bilamellar structures. The liposome formulations were well tolerated in the human breast adenocarcinoma (MCF-7) and colon carcinoma (HT-29) cells, which overexpress c-myc. Lipoplexes directed against the c-myc transcript mediated a dramatic reduction in c-myc mRNA and protein levels. Moreover, oncogene knockdown and anti-cancer effects were superior to that of Lipofectamine™ 3000. Conclusion: This anti-c-myc MS09:Chol lipoplex exemplifies a simple anticancer agent with enhanced c-myc gene silencing potential in vitro.

scholarly journals pH-sensitive zwitterionic polycarboxybetaine as a potential non-viral vector for small interfering RNA delivery

RSC Advances ◽  
2020 ◽  
Vol 10 (73) ◽  
pp. 45059-45066
Author(s):  
Huan Peng ◽  
Weihong Ji ◽  
Ruichen Zhao ◽  
Zhiguo Lu ◽  
Jun Yang ◽  
...  
Keyword(s):  
Small Interfering Rna ◽  
Viral Vector ◽  
Sirna Delivery ◽  
Ph Sensitive ◽  
Acidic Environment ◽  
Interfering Rna

pH-sensitive zwitterionic polycarboxybetaine could complex siRNA in an acidic environment and could be used as a non-viral vector for safe siRNA delivery.

scholarly journals Low-Molecular-Weight Polyethyleneimine Grafted Polythiophene for Efficient siRNA Delivery

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Pan He ◽  
Kyoji Hagiwara ◽  
Hui Chong ◽  
Hsiao-hua Yu ◽  
Yoshihiro Ito
Keyword(s):  
Molecular Weight ◽  
Sirna Delivery ◽  
Fluorescent Microscopy ◽  
Molar Ratio ◽  
Low Molecular Weight ◽  
Label Free ◽  
Endosomal Membrane ◽  
Cationic Copolymers ◽  
Interfering Rna

Owing to its hydrophilicity, negative charge, small size, and labile degradation by endogenous nucleases, small interfering RNA (siRNA) delivery must be achieved by a carrier system. In this study, cationic copolymers composed of low-molecular-weight polyethylenimine and polythiophenes were synthesized and evaluated as novel self-tracking siRNA delivery vectors. The concept underlying the design of these copolymers is that hydrophobicity and rigidity of polythiophenes should enhance the transport of siRNA across the cell membrane and endosomal membrane. A gel retardation assay showed that the nanosized complexes formed between the copolymers and siRNA were stable even at a molar ratio of 1 : 2. The high cellular uptake (>80%) and localization of the copolymer vectors inside the cells were easily analyzed by tracking the fluorescence of polythiophene using fluorescent microscopy and cytometry. Anin vitroluciferase knockdown (KD) assay in A549-luc cells demonstrated that the siRNA complexes with more hydrophobic copolymers achieved a higher KD efficiency of 52.8% without notable cytotoxicity, indicating protein-specific KD activity rather than solely the cytotoxicity of the materials. Our polythiophene copolymers should serve as novel, efficient, low cell toxicity, and label-free siRNA delivery systems.

scholarly journals Structurally modulated codelivery of siRNA and Argonaute 2 for enhanced RNA interference

2018 ◽  
Vol 115 (12) ◽  
pp. E2696-E2705 ◽  
Author(s):  
Jiahe Li ◽  
Connie Wu ◽  
Wade Wang ◽  
Yanpu He ◽  
Elad Elkayam ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Rna Interference ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Effector Protein ◽  
Side Group ◽  
Argonaute 2 ◽  
Fundamental Research ◽  
Delivery Vehicles ◽  
Interfering Rna

Small interfering RNA (siRNA) represents a promising class of inhibitors in both fundamental research and the clinic. Numerous delivery vehicles have been developed to facilitate siRNA delivery. Nevertheless, achieving highly potent RNA interference (RNAi) toward clinical translation requires efficient formation of RNA-induced gene-silencing complex (RISC) in the cytoplasm. Here we coencapsulate siRNA and the central RNAi effector protein Argonaute 2 (Ago2) via different delivery carriers as a platform to augment RNAi. The physical clustering between siRNA and Ago2 is found to be indispensable for enhanced RNAi. Moreover, by utilizing polyamines bearing the same backbone but distinct cationic side-group arrangements of ethylene diamine repeats as the delivery vehicles, we find that the molecular structure of these polyamines modulates the degree of siRNA/Ago2-mediated improvement of RNAi. We apply this strategy to silence the oncogene STAT3 and significantly prolong survival in mice challenged with melanoma. Our findings suggest a paradigm for RNAi via the synergistic coassembly of RNA with helper proteins.

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