scholarly journals Rationale and Application of PEGylated Lipid-Based System for Advanced Target Delivery of siRNA

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuemei Ge ◽  
Lijuan Chen ◽  
Bo Zhao ◽  
Weien Yuan
Keyword(s):  
Delivery System ◽  
High Efficiency ◽  
Sirna Delivery ◽  
High Specificity ◽  
Life Time ◽  
Delivery Systems ◽  
Target Delivery ◽  
Rnai Technology ◽  
Targeting Delivery

RNA interference (RNAi) technology has become a powerful tool in application of unraveling the mechanism of disease and may hold the potential to be developed for clinical uses. Small interfering RNA (siRNA) can bind to target mRNA with high specificity and efficacy and thus inhibit the expression of related protein for the purpose of treatment of diseases. The major challenge for RNAi application is how to improve its stability and bioactivity and therefore deliver therapeutic agents to the target sites with high efficiency and accuracy. PEGylated lipid-based delivery system has been widely used for development of various medicines due to its long circulating half-life time, low toxicity, biocompatibility, and easiness to be scaled up. The PEGylated lipid-based delivery system may also provide platform for targeting delivery of nucleic acids, and some of the research works have moved to the phases for clinical trials. In this review, we introduced the mechanism, major challenges, and strategies to overcome technical barriers of PEGylated lipid-based delivery systems for advanced target delivery of siRNA in vivo. We also summarized recent advance of PEGylated lipid-based siRNA delivery systems and included some successful research works in this field.

scholarly journals Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2570 ◽  
Author(s):  
Inés Serrano-Sevilla ◽  
Álvaro Artiga ◽  
Scott G. Mitchell ◽  
Laura De Matteis ◽  
Jesús M. de la Fuente
Keyword(s):  
Drug Delivery ◽  
Hyaluronic Acid ◽  
Small Interfering Rna ◽  
Drug Delivery Systems ◽  
Sirna Delivery ◽  
Delivery Systems ◽  
Low Toxicity ◽  
Interfering Rna

Natural polysaccharides are frequently used in the design of drug delivery systems due to their biocompatibility, biodegradability, and low toxicity. Moreover, they are diverse in structure, size, and charge, and their chemical functional groups can be easily modified to match the needs of the final application and mode of administration. This review focuses on polysaccharidic nanocarriers based on chitosan and hyaluronic acid for small interfering RNA (siRNA) delivery, which are highly positively and negatively charged, respectively. The key properties, strengths, and drawbacks of each polysaccharide are discussed. In addition, their use as efficient nanodelivery systems for gene silencing applications is put into context using the most recent examples from the literature. The latest advances in this field illustrate effectively how chitosan and hyaluronic acid can be modified or associated with other molecules in order to overcome their limitations to produce optimized siRNA delivery systems with promising in vitro and in vivo results.

scholarly journals Novel Surface Modification of ZnO QDs for Paclitaxel-Targeted Drug Delivery for Lung Cancer Treatment

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582092673
Author(s):  
Chuan Xie ◽  
Yan Zhan ◽  
Peng Wang ◽  
Bo Zhang ◽  
Yukun Zhang
Keyword(s):  
Drug Delivery ◽  
Surface Modification ◽  
Cancer Treatment ◽  
Drug Delivery System ◽  
Delivery System ◽  
High Efficiency ◽  
A549 Cells ◽  
Cytotoxicity Studies

Adipic dihydrazide and heparin were attached to ZnO quantum dots surface, and the ZnO-adipic dihydrazide-heparin nanocomplex was used as a drug delivery system to deliver paclitaxel for chemotherapy. The surface modification and the loading of paclitaxel were confirmed by Fourier transform infrared spectrum, featured by characteristic peaks from functional groups of adipic dihydrazide, heparin, and paclitaxel. The impacts of pH on the drug release were investigated, and the cytotoxicity studies were conducted with A549 cells. The pharmacokinetic study was conducted with male Wistar rats. Both in vitro and in vivo study indicated that ZnO-adipic dihydrazide-heparin-paclitaxel nanocomplex could deliver paclitaxel in a more controllable way, and it has the potential to be a high-efficiency drug delivery system for cancer treatment.

scholarly journals Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome

2020 ◽  
Vol 6 (30) ◽  
pp. eaba5379 ◽  
Author(s):  
Md. Nazir Hossen ◽  
Lin Wang ◽  
Harisha R. Chinthalapally ◽  
Joe D. Robertson ◽  
Kar-Ming Fung ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gold Nanoparticles ◽  
Gene Silencing ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Delivery Systems ◽  
Ovarian Cancer Cells ◽  
Interfering Rna

Gene silencing using small-interfering RNA (siRNA) is a viable therapeutic approach; however, the lack of effective delivery systems limits its clinical translation. Herein, we doped conventional siRNA-liposomal formulations with gold nanoparticles to create “auroliposomes,” which significantly enhanced gene silencing. We targeted MICU1, a novel glycolytic switch in ovarian cancer, and delivered MICU1-siRNA using three delivery systems—commercial transfection agents, conventional liposomes, and auroliposomes. Low-dose siRNA via transfection or conventional liposomes was ineffective for MICU1 silencing; however, in auroliposomes, the same dose gave >85% gene silencing. Efficacy was evident from both in vitro growth assays of ovarian cancer cells and in vivo tumor growth in human ovarian cell line—and patient-derived xenograft models. Incorporation of gold nanoparticles shifted intracellular uptake pathways such that liposomes avoided degradation within lysosomes. Auroliposomes were nontoxic to vital organs. Therefore, auroliposomes represent a novel siRNA delivery system with superior efficacy for multiple therapeutic applications.

scholarly journals Novel siRNA Delivery System to Target Podocytes In Vivo

PLoS ONE ◽  
2010 ◽  
Vol 5 (3) ◽  
pp. e9463 ◽  
Author(s):  
Peter V. Hauser ◽  
Jeffrey W. Pippin ◽  
Cora Kaiser ◽  
Ronald D. Krofft ◽  
Paul T. Brinkkoetter ◽  
...  
Keyword(s):  
Delivery System ◽  
Sirna Delivery ◽  
Sirna Delivery System

scholarly journals Sphingosomes: A Novel Lipoidal Vesicular Drug Delivery System

2020 ◽  
pp. 261-267
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Chemotherapeutic Agents ◽  
Biological Macromolecules ◽  
Area Of Interest ◽  
Aqueous Volume

Vesicular drug delivery system has various advantages thereby improving therapeutic efficacy and by sustaining and controlling action of drugs. Liposomes, sphingosomes, ethosomes, cubosomes, pharmacasomes, niosomes, transferosomes are the newly developed vesicular drug delivery system. This review article mainly deals with the sphingosomal drug delivery system. Sphingosomes are vesicular drug delivery systems in which an aqueous volume is enclosed with sphingolipid bilayer membranes. Sphingosomes has an enhanced area of interest because of their applicability in improving the in vivo delivery of various chemotherapeutic agents, biological macromolecules and diagnostics. Sphingosome has major advantages over other vesicular drug delivery systems like high stability, more in vivo circulation time, high tumor loading efficacy in case of cancer therapy as compared to liposomes, niosomes etc. Sphingosomes are clinically used vesicular delivery system for chemotherapeutic agent, biological macromolecule and diagnostics. This review concluded that sphingosome represents a promising vesicular drug delivery system for a range of possible therapeutic applications.

Solid self-emulsifying drug delivery system (Solid SEDDS) for testosterone undecanoate: in vitro and in vivo evaluation

2020 ◽  
Vol 17 ◽  
Author(s):  
Xi Liang ◽  
Yabing Hua ◽  
Qian Liu ◽  
Zhiguo Li ◽  
Fanglin Yu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Drug Delivery ◽  
Delivery System ◽  
High Fat Diet ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
High Fat ◽  
Testosterone Undecanoate

Objective: The current study aimed to investigate the potential of solid self-emulsifying drug delivery systems (solid SEDDS) loaded with testosterone undecanoate (TU) (solid TU-SEDDS). The solid TU-SEDDS was composed of TU, medium-chain triglycerides (MCT, oil), 2-Chloro-1-(chloromethyl) ethyl carbamate (EL-35, surfactant) and polyethylene glycol (PEG400, cosurfactant). It was expected to improve the dissolution and oral bioavailability of TU, as a result of investigating the feasibility of clinical application of SEDDS. Methods: First, a TU-SEDDS was developed by using rational blends of components with good solubilizing ability for TU. Next, a ternary phase diagram was constructed to determine the self-emulsifying region, and the formulation was optimized. Then, the solid TU-SEDDS formulation was established by screening suitable solid adsorptions. Finally, the prepared SEDDS, TU-SEDDS and solid TU-SEDDS formulations were evaluated in vitro and in vivo. Results: The size of the solid TU-SEDDS was 189.1 ± 0.23 nm. The transmission electron microscopy (TEM) results showed that the oil droplets were homogenous and spherical with good integrity. The differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) results indicated that the solid TU-SEDDS formulation almost preserves the amorphous state. Scanning electron microscopy (SEM) indicated that neusilin US2 successfully adsorbed the TU-SEDDS. Drug release indicated that the dissolution of the solid TU-SEDDS was faster than that of Andriol Testocaps®. Furthermore, in vivo pharmacokinetic (PK) studies in Sprague-Dawley (SD) rats showed that the area under the curve (AUC) of the solid TU-SEDDS (487.54±208.80 µg/L×h) was higher than that of Andriol Testocaps® (418.93±273.52 µg/L×h, P < 0.05). In beagles not fed a high-fat diet, the AUC of the solid TU-SEDDS (5.81±4.03 µg/L×h) was higher than that of Andriol Testocaps® (5.53±3.43 µg/L×h, P > 0.05). In beagles fed a high-fat diet, the AUC of the solid TU-SEDDS (38.18±21.90 µg/L×h) was higher than that of Andriol Testocaps® (37.17±13.79 µg/L×h, P > 0.05). Conclusion: According to the results of this research, oral solid TU-SEDDS is expected to be another alternative delivery system for the late-onset hypogonadism. This is beneficial to the transformation of existing drug delivery systems into preclinical and clinical studies.

RNase non-sensitive and endocytosis independent siRNA delivery system: delivery of siRNA into tumor cells and high efficiency induction of apoptosis

Nanoscale ◽  
2013 ◽  
Vol 5 (16) ◽  
pp. 7256 ◽  
Author(s):  
Xinglu Jiang ◽  
Guobao Wang ◽  
Ru Liu ◽  
Yaling Wang ◽  
Yongkui Wang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Delivery System ◽  
High Efficiency ◽  
Sirna Delivery ◽  
Induction Of Apoptosis ◽  
Sirna Delivery System

scholarly journals Non-Viral Delivery and Therapeutic Application of Small Interfering RNAs

Acta Naturae ◽  
2013 ◽  
Vol 5 (3) ◽  
pp. 35-53 ◽  
Author(s):  
N. A. Nikitenko ◽  
V. S. Prassolov
Keyword(s):  
Rna Interference ◽  
Gene Expression Regulation ◽  
Sirna Delivery ◽  
Target Cells ◽  
Powerful Method ◽  
Small Interfering Rnas ◽  
Therapeutic Application ◽  
Rnai Technology ◽  
In Vivo Degradation

RNA interference (RNAi) is a powerful method used for gene expression regulation. The increasing knowledge about the molecular mechanism of this phenomenon creates new avenues for the application of the RNAi technology in the treatment of various human diseases. However, delivery of RNA interference mediators, small interfering RNAs (siRNAs), to target cells is a major hurdle. Effective and safe pharmacological use of siRNAs requires carriers that can deliver siRNA to its target site and the development of methods for protection of these fragile molecules from in vivo degradation. This review summarizes various strategies for siRNA delivery, including chemical modification and non-viral approaches, such as the polymer-based, peptide-based, lipid-based techniques, and inorganic nanosystems. The advantages, disadvantages, and prospects for the therapeutic application of these methods are also examined in this paper.

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