scholarly journals Nanomaterials-Based siRNA Delivery: Routes of Administration, Hurdles and Role of Nanocarriers

Author(s):  
Nitin Gupta ◽  
Divya Bharti Rai ◽  
Ashok Kumar Jangid ◽  
Deep Pooja ◽  
Hitesh Kulhari
2020 ◽  
Vol 27 (17) ◽  
pp. 2887-2901 ◽  
Author(s):  
Stacey Bartlett ◽  
Mariusz Skwarczynski ◽  
Istvan Toth

Background: Innate immune system plays an important role in pathogen detection and the recognition of vaccines, mainly through pattern recognition receptors (PRRs) that identify pathogen components (danger signals). One of the typically recognised bacterial components are lipids in conjugation with peptides, proteins and saccharides. Lipidic compounds are readily recognised by the immune system, and thus are ideal candidates for peptide- based vaccine delivery. Thus, bacterial or synthetic lipids mixed with, or conjugated to, antigens have shown adjuvant properties. These systems have many advantages over traditional adjuvants, including low toxicity and good efficacy for stimulating mucosal and systemic immune responses. Methods: The most recent literature on the role of lipids in stimulation of immune responses was selected for this review. The vast majority of reviewed papers were published in the last decade. Older but significant findings are also cited. Results: This review focuses on the development of lipopeptide vaccine systems including application of palmitic acid, bacterial lipopeptides, glycolipids and the lipid core peptide and their routes of administration. The use of liposomes as a delivery system that incorporates lipopeptides is discussed. The review also includes a brief description of immune system in relation to vaccinology and discussion on vaccine delivery routes. Conclusion: Lipids and their conjugates are an ideal frontrunner in the development of safe and efficient vaccines for different immunisation routes.


2020 ◽  
Vol 8 (2) ◽  
pp. 79-90
Author(s):  
Arjun Sharma ◽  
Pravir Kumar ◽  
Rashmi K. Ambasta

Background: Silencing of several genes is critical for cancer therapy. These genes may be apoptotic gene, cell proliferation gene, DNA synthesis gene, etc. The two subunits of Ribonucleotide Reductase (RR), RRM1 and RRM2, are critical for DNA synthesis. Hence, targeting the blockage of DNA synthesis at tumor site can be a smart mode of cancer therapy. Specific targeting of blockage of RRM2 is done effectively by SiRNA. The drawbacks of siRNA delivery in the body include the poor uptake by all kinds of cells, questionable stability under physiological condition, non-target effect and ability to trigger the immune response. These obstacles may be overcome by target delivery of siRNA at the tumor site. This review presents a holistic overview regarding the role of RRM2 in controlling cancer progression. The nanoparticles are more effective due to specific characteristics like cell membrane penetration capacity, less toxicity, etc. RRM2 have been found to be elevated in different types of cancer and identified as the prognostic and predictive marker of the disease. Reductase RRM1 and RRM2 regulate the protein and gene expression of E2F, which is critical for protein expression and progression of cell cycle and cancer. The knockdown of RRM2 leads to apoptosis via Bcl2 in cancer. Both Bcl2 and E2F are critical in the progression of cancer, hence a gene that can affect both in regulating DNA replication is essential for cancer therapy. Aim: The aim of the review is to identify the related gene whose silencing may inhibit cancer progression. Conclusion: In this review, we illuminate the critical link between RRM-E2F, RRM-Bcl2, RRM-HDAC for the therapy of cancer. Altogether, this review presents an overview of all types of SiRNA targeted for cancer therapy with special emphasis on RRM2 for controlling the tumor progression.


Nanoscale ◽  
2018 ◽  
Vol 10 (23) ◽  
pp. 10952-10962 ◽  
Author(s):  
Marco A. Deriu ◽  
Nicolas Tsapis ◽  
Magali Noiray ◽  
Gianvito Grasso ◽  
Nabil El Brahmi ◽  
...  

In the field of dendrimers targeting small interfering RNA (siRNA) delivery, dendrimer structural properties, such as the surface chemistry, play a crucial role in the efficiency of complexation.


Nanomedicine ◽  
2021 ◽  
Author(s):  
Dongyu Chen ◽  
Shanthi Ganesh ◽  
Weimin Wang ◽  
Adrien Lupieri ◽  
Mansoor Amiji

Aim: To evaluate the role of vitronectin-enriched protein corona on systemic delivery of siRNA-encapsulated cationic lipid nanoparticles (LNPs) to αvβ3 integrin expressing solid tumors. Materials & methods: 1,2-Dioleoyl-3-trimethylammonium-propane LNPs were formulated, protein corona formed in nude mice serum and its impact on drug delivery were analyzed. Results: 1,2-Dioleoyl-3-trimethylammonium-propane-containing LNP led to enhanced recruitment of vitronectin and showed preferential transfection to αvβ3-expressed cells relative to controls. Upon systemic administration in mice, the LNPs accumulated in the αvβ3-expressing endothelial lining of the tumor blood vessels before reaching tumor cells. Conclusion: These results present an optimized LNP that selectively recruits endogenous proteins in situ to its corona which may lead to enhanced delivery and transfection in tissues of interest.


Author(s):  
Rafael Maldonado ◽  
Diego Centonze ◽  
Kirsten Muller-Vahl

The perception of cannabis in society has changed over the last decades, leading to an increasing permissiveness about its use mainly across Western countries. This has happened in parallel to the growing study of the possible role of cannabinoid-based products in medicine. The cannabis plant contents comprise more than one hundred different cannabinoids, each binding differently to numerous human body targets. This cannabinoids administration, either isolated, combining some of them, or as a full plant extract can produce many different risk–benefit effects in humans depending on the product composition. Moreover, we have seen the appearance of synthetic cannabinoids. As expected, doses and different routes of administration introduce further variability. Cannabinoid-based pharmaceutical products authorised for medicinal use after comprehensive research and with approval by regulatory medicines agencies, such as the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA), should be distinguished from cannabinoid-based products (whether standardised or not) that aimed for medicinal use but lack submitted efficacy, tolerability, and safety scientific evidence for regulatory approval. Distribution of some of the latter products are still allowed in certain geographical areas. There are also cannabinoid products used mainly recreationally or as food supplements and ruled separately. In a detailed white paper, this review describes the present situation, depicting the societal and medical state of the art, collecting the facts-based risk–benefit features of already available cannabinoid-based products, and also the future possibilities in medicine, which can be vast if proper research is developed


2012 ◽  
Vol 19 (29) ◽  
pp. 4929-4941 ◽  
Author(s):  
G. M. Pavan ◽  
S. Monteagudo ◽  
J. Guerra ◽  
B. Carrion ◽  
V. Ocana ◽  
...  

2016 ◽  
Vol 235 ◽  
pp. 99-111 ◽  
Author(s):  
Xiao-Fei Ma ◽  
Jing Sun ◽  
Chong Qiu ◽  
Yi-Fan Wu ◽  
Yi Zheng ◽  
...  

2021 ◽  
pp. 0271678X2110008
Author(s):  
Cellas A Hayes ◽  
M Noa Valcarcel-Ares ◽  
Nicole M Ashpole

Ischemic strokes are highly prevalent in the elderly population and are a leading cause of mortality and morbidity worldwide. The risk of ischemic stroke increases in advanced age, corresponding with a noted decrease in circulating insulin growth factor-1 (IGF-1). IGF-1 is a known neuroprotectant involved in embryonic development, neurogenesis, neurotransmission, cognition, and lifespan. Clinically, several studies have shown that reduced levels of IGF-1 correlate with increased mortality rate, poorer functional outcomes, and increased morbidities following an ischemic stroke. In animal models of ischemia, administering exogenous IGF-1 using various routes of administration (intranasal, intravenous, subcutaneous, or topical) at various time points prior to and following insult attenuates neurological damage and accompanying behavioral changes caused by ischemia. However, there are some contrasting findings in select clinical and preclinical studies. This review discusses the role of IGF-1 as a determinant factor of ischemic stroke outcomes, both within the clinical settings and preclinical animal models. Furthermore, the review provides insight on the role of IGF-1 in mechanisms and cellular processes that contribute to stroke damage.


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