Oral Administration of ginger-derived Nanolipids Loaded With siRNA As a Novel Approach for Efficient siRNA Drug Delivery to Treat Ulcerative Colitis

Zhang, Mingzhen; Wang, Xiaoyu; Han, Moon Kwon; Collins, James F.; Merlin, Didier

doi:10.2217/nnm-2017-0196

Cited by 201 publications

(210 citation statements)

References 46 publications

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“…For biologics, the traditional delivery route is the intravenous injection; however, recent advances in plant-derived NPs have demonstrated that GDLPs could orally deliver CD98 siRNAs to the inflamed colon, offering a new approach for orally delivering biologics to treat IBD. 102 Although many small molecules may be delivered to the colon by NPs, efforts should be made to prevent the premature drug release caused by acidic erosion in the stomach and enzymatic degradation along the GI tract. Enteric coatings or degradation-resistant NP delivery systems can potentially be used to protect encapsulated drugs.…”

Section: Oral Administrationmentioning

confidence: 99%

“…The lipid compositions differ drastically between plant-and animal cell-derived exosomes, but both exhibit equally powerful cell-specific targeting functions. For instance, ginger-derived lipid vesicles can specifically target IECs and deliver CD98 siRNA to reduce colonic CD98 gene expression, 102 while exosomes from antigenpresenting DC cells could activate both regulatory and helper T cells. 126 It has been suggested that these naturally occurring NPs could shift the current paradigm of NP drug delivery from using synthetic polymeric NPs to using natural NPs.…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

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<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

Yang¹,

Merlin²

2019

IJN

Self Cite

115

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Inflammatory bowel disease (IBD), which mainly consists of Crohn's disease and ulcerative colitis, is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The traditional treatment strategies relied on frequent administration of high dosages of medications, including antibiotics, non-steroidal anti-inflammatory drugs, biologics, and immunomodulators, with the goal of reducing inflammation. Some of these medications were effective in alleviating the early-stage inflammatory symptoms, but their long-term efficacies were compromised by the accumulation of toxicities. Recently, nanoparticle (NP)based drugs have been widely studied for their potential to solve such problems. Various mechanisms/strategies, including size-, charge-, pH-, pressure-, degradation-, ligand-receptor-, and microbiome-dependent drug delivery systems, have been exploited in preclinical studies. A certain number of NP delivery systems have sought to target drugs to the inflamed intestine. Although several NP-based drugs have entered clinical trials for the treatment of IBD, most have failed due to premature drug release, weak targeting ability, and the high immune toxicity of some of the synthetic nanomaterials that have been used to fabricate the NPs. Therefore, there is still a need for rationally designed and stable NP drug delivery system that can specifically target drugs to the disease site, prolong the drug's residence time, and minimize systemic side effects. This review will analyze the current state of the art in NP-mediated drug delivery for IBD treatment. We will focus on topics such as deliverable targets (at the tissue or cellular level) for treating inflammation; the target-homing NP materials that can interact with such targets; and the major administration routes for treating IBD. These discussions will integrate notable trends in the research and development of IBD medications, including multi-responsive NP-mediated delivery and naturally-derived targeting NPs. Finally, current challenges and future directions will be presented in the hopes of advancing the study of NP-mediated strategies for treating IBD.

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Section: Oral Administrationmentioning

confidence: 99%

Section: Conclusion and Prospectsmentioning

confidence: 99%

<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

Yang¹,

Merlin²

2019

IJN

Self Cite

115

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“…Fresh ginger juice can be used to afford, by a controlled methodology [92][93][94], ginger-derived nanoparticles (GDPs) that are suitable for loading and carrying APIs or other compounds. GDPs from ginger contain lipids, mainly phosphatidic acids (41.9% of total lipids), digalactosyldiacylglycerol (27.4%) and monogalactosyldiacylglycerol (18.9%) [95], as well as a fair amount of RNA [94]. GDPs have, thus, an intrinsic immunomodulatory activity, inducing production of the cytokines IL-6 and IL-10 when incubated with macrophages.…”

Section: Ginger-derived Nanoparticles (Gdps)mentioning

confidence: 99%

“…In vitro studies on the RAW 264.7 and colon-26 cell lines show successful transfection, with distribution of the GDPs throughout the cells and inhibition of the expression of CD98 gene by roughly 20% in colon-26 cells and 50% in RAW cells. The GDPs have also good distribution in vivo, with studies on mice demonstrating that they have a preferential action (CD98 knock-out) on the ileum and the colon [95].…”

Section: Ginger-derived Nanoparticles (Gdps)mentioning

confidence: 99%

Ginger: Panacea or Consumer’s Hype?

Braga

2019

Applied Sciences

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Ginger in its many forms, from juices of the fresh rhizome, to ginger powder and ginger essential oil, is growing in popularity for claimed universal health benefits. Nevertheless, and contrarily to the common notion of the public, ginger is not devoid of side effects, especially interactions with other drugs, and many of the claimed benefits remain to be substantiated. This work presents a comprehensive revision of the current state of the art on ginger pharmacokinetics and bioavailability, interaction with active pharmaceutical ingredients, raising awareness of the risks of uncontrolled ginger consumption. A second section of the work described the verified actions of various extracts of ginger, or of their main active ingredients, gingerols, based mainly on data obtained from controlled clinical trials. Finally, the last section is devoted to innovative technological solutions to improve the bioavailability of gingerols and ginger extracts that are expected to ultimately lead to the development of more consumer-compliant products.

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“…The toxicity of synthetic cationic liposomes makes the search for naturally sourced lipid delivery vehicles a promising field. Zhang et al . investigated nanoparticles fabricated from lipids harvested from ginger, termed ginger‐derived lipid vehicles (GDLV).…”

Section: Oral Delivery Systemsmentioning

confidence: 99%

siRNA Targeting and Treatment of Gastrointestinal Diseases

Chevalier

2019

Clinical Translational Sci

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RNA interference via small interfering RNA (siRNA) offers opportunities to precisely target genes that contribute to gastrointestinal (GI) pathologies, such as inflammatory bowel disease, celiac, and esophageal scarring. Delivering the siRNA to the GI tract proves challenging as the harsh environment of the intestines degrades the siRNA before it can reach its target or blocks its entry into its site of action in the cytoplasm. Additionally, the GI tract is large and disease is often localized to a specific site. This review discusses polymer and lipid‐based delivery systems for protection and targeting of siRNA therapies to the GI tract to treat local disease.

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Oral Administration of ginger-derived Nanolipids Loaded With siRNA As a Novel Approach for Efficient siRNA Drug Delivery to Treat Ulcerative Colitis

Cited by 201 publications

References 46 publications

<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

Ginger: Panacea or Consumer’s Hype?

siRNA Targeting and Treatment of Gastrointestinal Diseases

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