scholarly journals Oncogene dependency and the potential of targeted RNAi-based anti-cancer therapy

2014 ◽  
Vol 461 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Ruiyang Yan ◽  
Andrew Hallam ◽  
Peter G. Stockley ◽  
Joan Boyes
Keyword(s):  
Delivery Systems ◽  
Cationic Polymers ◽  
Anti Cancer ◽  
Invaluable Tool ◽  
Effective Delivery ◽  
Rnai Therapeutics ◽  
Delivery Strategies ◽  
High Immunogenicity

Cancers arise through the progression of multiple genetic and epigenetic defects that lead to deregulation of numerous signalling networks. However, the last decade has seen the development of the concept of ‘oncogene addiction’, where tumours appear to depend on a single oncogene for survival. RNAi has provided an invaluable tool in the identification of these oncogenes and oncogene-dependent cancers, and also presents great potential as a novel therapeutic strategy against them. Although RNAi therapeutics have demonstrated effective killing of oncogene-dependent cancers in vitro, their efficacy in vivo is severely limited by effective delivery systems. Several virus-based RNAi delivery strategies have been explored, but problems arose associated with high immunogenicity, random genome integration and non-specific targeting. This has directed efforts towards non-viral formulations, including delivery systems based on virus-like particles, liposomes and cationic polymers, which can circumvent some of these problems by immunomasking and the use of specific tumour-targeting ligands. This review outlines the prevalence of oncogene-dependent cancers, evaluates the potential of RNAi-based therapeutics and assesses the relative strengths and weaknesses of different approaches to targeted RNAi delivery.

Cytokine regulation of mucosal responses: a rational basis for new vaccine delivery strategies

1994 ◽  
Vol 6 (3) ◽  
pp. 381 ◽  
Author(s):  
AJ Husband ◽  
S Bao ◽  
W Muir ◽  
AJ Ramsay ◽  
IA Ramshaw
Keyword(s):  
Gene Therapy ◽  
Vaccine Delivery ◽  
Delivery Systems ◽  
Immune Network ◽  
Rational Basis ◽  
Cytokine Regulation ◽  
Host Environment ◽  
Delivery Strategies

In this review, cytokine regulation of mucosal responses is discussed in relation to the mucosal immune network and regulation of IgA responses. Based on this understanding, aspects of gene therapy for manipulation of the host environment and vaccine delivery systems are discussed. Although evidence obtained in vitro is briefly reviewed the general focus of this article is on evidence obtained from models in vivo.

scholarly journals miRNA- and lncRNA-Based Therapeutics for Non-Hodgkin’s Lymphoma: Moving towards an RNA-Guided Precision Medicine

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6324
Author(s):  
Mara Fernandes ◽  
Herlander Marques ◽  
Ana Luísa Teixeira ◽  
Rui Medeiros
Keyword(s):  
Standard Treatment ◽  
Delivery Systems ◽  
Functional Roles ◽  
Treatment Regimens ◽  
Novel Mirna ◽  
Different Types ◽  
Effective Delivery ◽  
Target Effects

Increasing evidence has demonstrated the functional roles of miRNAs and lncRNAs in lymphoma onset and progression, either by acting as tumor-promoting ncRNAs or as tumor suppressors, emphasizing their appeal as lymphoma therapeutics. In fact, their intrinsic ability to modulate multiple dysregulated genes and/or signaling pathways makes them an attractive therapeutic approach for a multifactorial pathology like lymphoma. Currently, the clinical application of miRNA- and lncRNA-based therapies still faces obstacles regarding effective delivery systems, off-target effects, and safety, which can be minimized with the appropriate chemical modifications and the development of tumor site-specific delivery approaches. Moreover, miRNA- and lncRNA-based therapeutics are being studied not only as monotherapies but also as complements of standard treatment regimens to provide a synergic effect, improving the overall treatment efficacy and reducing the therapeutic resistance. In this review, we summarize the fundamentals of miRNA- and lncRNA-based therapeutics by discussing the different types of delivery systems, with a focus on those that have been investigated in lymphoma in vitro and in vivo. Moreover, we described the ongoing clinical trials of novel miRNA- and lncRNA-based therapeutics in lymphoma.

Drug Delivery Systems For Anti-Cancer Active Complexes of Some Coinage Metals

2018 ◽  
Vol 25 (4) ◽  
pp. 493-505 ◽  
Author(s):  
Ming Zhang ◽  
Camille Saint-Germain ◽  
Guiling He ◽  
Raymond Wai-Yin Sun
Keyword(s):  
Drug Delivery ◽  
Metal Complexes ◽  
Drug Delivery Systems ◽  
Platinum Complexes ◽  
Delivery Systems ◽  
Development Of Resistance ◽  
Anti Cancer ◽  
Coinage Metals

Background: Although cisplatin and a number of platinum complexes have widely been used for the treatment of neoplasia, patients receiving these treatments have frequently suffered from their severe toxic side effects, the development of resistance with consequent relapse. In the recent decades, numerous complexes of coinage metals including that of gold, copper and silver have been reported to display promising in vitro and/or in vivo anti-cancer activities as well as potent activities towards cisplatin-resistant tumors. Nevertheless, the medical development of these metal complexes has been hampered by their instability in aqueous solutions and the nonspecific binding in biological systems. Methods: One of the approaches to overcome these problems is to design and develop adequate drug delivery systems (DDSs) for the transport of these complexes. By functionalization, encapsulation or formulation of the metal complexes, several types of DDSs have been reported to improve the desired pharmacological profile of the metal complexes, improving their overall stability, bioavailability, anti-cancer activity and reducing their toxicity towards normal cells. Conclusion: In this review, we summarized the recent findings for different DDSs for various anti- cancer active complexes of some coinage metals.

scholarly journals A nanoformulation of siRNA and its role in cancer therapy: In vitro and in vivo evaluation

2013 ◽  
Vol 18 (1) ◽  
Author(s):  
Hitesh Jagani ◽  
Josyula Rao ◽  
Vasanth Palanimuthu ◽  
Raghu Hariharapura ◽  
Sagar Gang
Keyword(s):  
Chitosan Nanoparticles ◽  
Cancer Drugs ◽  
Neoplastic Cells ◽  
In Vivo Evaluation ◽  
Anti Cancer ◽  
Effective Delivery ◽  
Interfering Rna ◽  
Cancerous Cells

AbstractOverexpression of anti-apoptotic Bcl-2 is often observed in a wide variety of human cancers. It prevents the induction of apoptosis in neoplastic cells and contributes to resistance to chemotherapy. RNA interference has emerged as an efficient and selective technique for gene silencing. The potential to use small interfering RNA (siRNA) as a therapeutic agent for the treatment of cancer has elicited a great deal of interest. However, insufficient cellular uptake and poor stability have limited its therapeutic applications. The purpose of this study was to prepare chitosan nanoparticles via ionic gelation of chitosan by tripolyphosphate for effective delivery of siRNA to silence the anti-apoptotic Bcl-2 gene in neoplastic cells. Chitosan nanoparticles loaded with siRNA were in the size range 190 to 340 nm with a polydispersive index ranging from 0.04 to 0.2. They were able to completely bind with siRNA, provide protection against nuclease degradation, and enhance the transfection. Cell culture studies revealed that nanoparticles with entrapped siRNA could efficiently silence the antiapoptotic Bcl-2 gene. Studies on Swiss albino mice showed that siRNA could be effectively delivered through nanoparticles. There was significant decrease in the tumor volume. Blocking the expression of anti-apoptotic Bcl-2 can enhance the sensitivity of cancerous cells to anti-cancer drugs and the apoptosis rate. Therefore, nanoformulations with siRNA can be promoted as an adjuvant therapy in combination with anti-cancer drugs.

scholarly journals A COMPREHENSIVE REVIEW ON SUPERSATURABLE SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM

2021 ◽  
pp. 40-44
Author(s):  
MUTHADI RADHIKA REDDY ◽  
KUMAR SHIVA GUBBIYAPPA
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
In Vitro Tests ◽  
Drug Bioavailability ◽  
Advantages And Disadvantages ◽  
Anti Cancer

Lipid-based drug delivery systems are extensively reported in the literature for enhancing drug solubility, permeability, and bioavailability. Self-nanoemulsifying drug delivery systems (SNEDDS) are a superior strategy for enhancing solubility and bioavailability of poorly water-soluble compounds and the most prevailing and commercially viable oil-based approach for drugs that exhibit low dissolution rate and inadequate absorption. However, these formulations have few limitations that include in vivo drug precipitation, inferior in vitro in vivo correlation owing to unavailability of in vitro tests, handling issues of liquid formulation, and physicochemical instability of drugs. These limitations are overcome by potential systems such as supersaturable SNEDDS (S-SNEDDS) which are prepared by addition of precipitation inhibitors into formulated SNEDDS to maintain drug supersaturation post dispersion in gastrointestinal tract. These systems improve drug bioavailability and reduce the inconsistency of exposure. In addition, these formulations also help to overcome the drawbacks of liquid and capsule dosage forms. The S-SNEDDS provides an effective approach for improving the dissolution and bioavailability of anti-cancer agents. In this article, an attempt was made to present an overview of SNEDDS, S-SNEDDS, their mechanism, formulation excipients, recent advancements, advantages, and disadvantages of SNEDDS formulations. The article also focuses on reviewing the application of S-SNEDDS in enhancing the solubility and bioavailability of anti-cancer drugs in cancer therapy.

scholarly journals Development of Flexible Polycation-Based mRNA Delivery Systems for In Vivo Applications

2020 ◽  
Vol 4 (1) ◽  
pp. 5
Author(s):  
Takuya Miyazaki ◽  
Satoshi Uchida ◽  
Yuji Miyahara ◽  
Akira Matsumoto ◽  
Horacio Cabral
Keyword(s):  
Gene Expression ◽  
Protein Translation ◽  
Delivery Systems ◽  
Systemic Injection ◽  
Broad Application ◽  
Effective Delivery ◽  
The Impact ◽  
Delivery Efficiency

mRNA is a promising therapeutic nucleic acid, although effective delivery systems are required for its broad application. Polyion complex (PIC) micelles loading mRNA via polyion complexation with block catiomers are emerging as promising carriers for mRNA delivery, but the PIC stability has been limited so far. Controlling the binding of polycations to mRNA could affect the micelle stability. Nevertheless, the impact of binding affinity between polycations and mRNA on the function of mRNA-loaded PIC micelles (mRNA/m) remains unknown. Herein, we review our recent orthogonal approaches controlling the stiffness and the valency of polycations to improve the performance of mRNA/m toward enhancing stability and delivery efficiency. Thus, block catiomers with contrasting flexibility were developed to prepare mRNA/m. The flexible catiomer stabilized mRNA/m against enzymatic attack and polyanion exchange compared to the rigid catiomer, promoting protein translation in vitro and in vivo, and prolonged mRNA bioavailability in blood after systemic injection. Based on these observations, we also developed flexible catiomers with different valencies. The guanidinated catiomer stabilized mRNA/m compared to the aminated catiomers, facilitating intracellular delivery and eventual gene expression. Our findings indicate the importance of controlling the polymer binding to mRNA for developing flexible polycation-based systems directed to in vivo applications.

FM2-6 Cell delivery for intracerebral cell transplantation

2019 ◽  
Vol 90 (3) ◽  
pp. e25.1-e25
Author(s):  
MAH Abdulla ◽  
AP Jathoul ◽  
AE Rosser ◽  
WP Gray
Keyword(s):  
Cell Transplantation ◽  
Delivery Systems ◽  
Large Animal Model ◽  
Large Animal ◽  
List Type ◽  
Agarose Gel ◽  
Contributing Factors ◽  
Delivery Strategies

ObjectivesClinical trials of intracerebral cell replacement therapy (CRT) yield inconsistent results owing to poor graft survival and ectopic graft placement. A paucity of available CE marked specialised delivery systems and a lack of reliable delivery protocols could be major contributing factors to both phenomena. Here, we aimed to investigate current needle delivery strategies in-vitro and in a large animal model in pigs.DesignIn-vitro laboratory and in-vivo pigs experiments.SubjectsIn-vitroAgarose gel In-vivo: 4 white Landracer pigs.MethodsIn-vitro: Human Embryonic Kidney cells expressing luciferase and 0.6% agarose gel were used to test 3 delivery strategies:Bracelet deposit,Large deposit in a pre–formed tract,Multiple deposits in a pre–formed tract.In-vivo: Pigs underwent MRI- guided Human Foetal Luciferase-transduced cell transplantation into the putamen and thalamus. Post-operative MRI, Bioluminescence imaging (BLI) and histology were used to identify graft location and viability.ResultsUsing a commercially available needle delivery system, significant reflux of deposits was noted in all 3 delivery strategies during in-vitro testing. Depositing into a preformed tract yielded the best delivery, and was therefore used for in-vivo testing. Studies in pigs using MRI and BLI confirmed significant reflux and ectopic deposition of grafts.ConclusionsSimple needle delivery systems appear to suffer from significant reflux and ectopic cell deposition. This may adversely affect the outcomes of CRT trials in humans.

Ethnomedicinal uses, Phytochemistry and Pharmacological Aspects of the Genus Berberis Linn: A Comprehensive Review

2020 ◽  
Vol 23 ◽  
Author(s):  
Roohi Mohi-ud-din ◽  
Reyaz Hassan Mir ◽  
Prince Ahad Mir ◽  
Saeema Farooq ◽  
Syed Naiem Raza ◽  
...  
Keyword(s):  
Chemical Constituents ◽  
Pharmacological Activities ◽  
Traditional Use ◽  
Comprehensive Review ◽  
Wide Range ◽  
Anti Cancer ◽  
Comprehensive Survey ◽  
Ethnomedicinal Uses

Background: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations. Objective: The present review is focussed to summarize and collect the updated review of information of Genus Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis. Conclusion: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, anti-inflammatory both in vitro & in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use.

Ferula hermonis: A Review of Current Use and Pharmacological Studies of its Sesquiterpene Ester Ferutinin

2020 ◽  
Vol 21 (5) ◽  
pp. 499-508 ◽  
Author(s):  
Rémi Safi ◽  
Marwan El-Sabban ◽  
Fadia Najjar
Keyword(s):  
Wide Spectrum ◽  
Endemic Plant ◽  
Anti Cancer ◽  
Pharmacological Studies ◽  
Sexual Impotence ◽  
Novel Applications ◽  
Anti Fungal ◽  
Sesquiterpene Ester

Ferula hermonis Boiss, is an endemic plant of Lebanon, locally known as “shilsh Elzallouh”. It has been extensively used in the traditional medicine as an aphrodisiac and for the treatment of sexual impotence. Crude extracts and isolated compounds of ferula hermonis contain phytoestrogenic substances having a wide spectrum of in vitro and in vivo pharmacological properties including anti-osteoporosis, anti-inflammatory, anti-microbial and anti-fungal, anti-cancer and as sexual activity enhancer. The aim of this mini-review is to highlight the traditional and novel applications of this plant’s extracts and its major sesquiterpene ester, ferutinin. The phytochemical constituents and the pharmacological uses of ferula hermonis crude extract and ferutinin specifically will be discussed.

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