Displaying all 14 publications

  1. Tekade RK
    Curr Pharm Des, 2015;21(31):4527-8.
    PMID: 26362643
    Matched MeSH terms: RNA, Small Interfering/administration & dosage*
  2. Chowdhury EH
    Expert Opin Drug Deliv, 2011 Mar;8(3):389-401.
    PMID: 21314230 DOI: 10.1517/17425247.2011.554817
    Current treatment of malignant tumors relies predominantly on chemotherapy delivering a single antineoplastic drug or a combination of two or more drugs intravenously. Problems with such treatments can include the killing of healthy cells, adverse side effects and chemoresistance. As cancer basically results from different types of mutation leading to the overexpression or suppression of the signaling cascades responsible for cancer cell survival and proliferation, tailor-made approaches capable of interfering precisely with those pathways are the potential revolutionary tools that could pave the way for highly effective cancer therapy.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage*
  3. Jain A, Jain A, Parajuli P, Mishra V, Ghoshal G, Singh B, et al.
    Drug Discov Today, 2018 05;23(5):960-973.
    PMID: 29129804 DOI: 10.1016/j.drudis.2017.11.003
    Galactosylated nanocarriers have recently emerged as viable and versatile tools to deliver drugs at an optimal rate specifically to their target tissues or cells, thus maximizing their therapeutic benefits while circumventing off-target effects. The abundance of lectin receptors on cell surfaces makes the galactosylated carriers suitable for the targeted delivery of bioactives. Additionally, tethering of galactose (GAL) to various carriers, including micelles, liposomes, and nanoparticles (NPs), might also be appropriate for drug delivery. Here, we review recent advances in the development of galactosylated nanocarriers for active tumor targeting. We also provide a brief overview of the targeting mechanisms and cell receptor theory involved in the ligand-receptor-mediated delivery of drug carriers.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage*
  4. Maheshwari R, Tekade M, Sharma PA, Tekade RK
    Curr Pharm Des, 2015;21(30):4427-40.
    PMID: 26471319
    Cardiovascular diseases (CVDs), primarily myocardial infarction (MI), atherosclerosis, hypertension and congestive heart failure symbolize the foremost cause of death in almost all parts of the world. Besides the traditional therapeutic approaches for the management of CVDs, newer innovative strategies are also emerging on the horizon. Recently, gene silencing via small interfering RNA (siRNA) is one of the hot topics amongst various strategies involved in the management of CVDs. The siRNA mechanism involves natural catalytic processes to silence pathological genes that are overexpressed in a particular disease. Also the versatility of gene expression by siRNA deciphers a prospective tactic to down-regulate diseases associated gene, protein or receptor existing on a specific disease target. This article reviews the application of siRNA against CVDs with special emphasis on gene targets in combination with delivery systems such as cationic hydrogels, polyplexes, peptides, liposomes and dendrimers.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage*
  5. Tekade RK, Maheshwari RG, Sharma PA, Tekade M, Chauhan AS
    Curr Pharm Des, 2015;21(31):4614-36.
    PMID: 26486147
    siRNA technology presents a helpful means of gene silencing in mammalian cells. Advancement in the field includes enhanced attentiveness in the characterization of target and off-target effects employing suitable controls and gene expression microarrays. These will permit expansion in the measurement of single and multiple target combinations and also permit comprehensive efforts to understand mammalian cell processes. Another fact is that the delivery of siRNA requires the creation of a nanoparticulate vector with controlled structural geometry and surface modalities inside the targeted cells. On the other hand, dendrimers represent the class of carrier system where massive control over size, shape and physicochemical properties makes this delivery vector exceptional and favorable in genetic transfection applications. The siRNA therapeutics may be incorporated inside the geometry of the density controlled dendrimers with the option of engineering the structure to the specific needs of the genetic material and its indication. The existing reports on the siRNA carrying and deliverance potential of dendrimers clearly suggest the significance of this novel class of polymeric architecture and certainly elevate the futuristic use of this highly branched vector as genetic material delivery system.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage*
  6. Katas H, Abdul Ghafoor Raja M, Ee LC
    Drug Dev Ind Pharm, 2014 Nov;40(11):1443-50.
    PMID: 23962166 DOI: 10.3109/03639045.2013.828222
    Recently, a newly discovered Dicer-substrate siRNA (DsiRNA) demonstrates higher potency in gene silencing than siRNA but both suffer from rapid degradation, poor cellular uptake and chemical instability. Therefore, Tat-peptide was exploited to protect and facilitate their delivery into cells. In this study, Tat-peptide was complexed with siRNA or DsiRNA through simple complexation. The physicochemical properties (particle size, surface charge and morphology) of the complexes formed were then characterized. The ability of Tat-peptide to carry and protect siRNA or DsiRNA was determined by UV-Vis spectrophotometry and serum protection assay, respectively. Cytotoxicity effect of these complexes was assessed in V79 cell line. siRNA-Tat complexes had particle size ranged from 186 ± 17.8 to 375 ± 8.3 nm with surface charge ranged from -9.3 ± 1.0 to +13.5 ± 1.0 mV, depending on the Tat-to-siRNA concentration ratio. As for DsiRNA-Tat complexes, the particle size was smaller than the ones complexed with siRNA, ranging from 176 ± 8.6 to 458 ± 14.7 nm. Their surface charge was in the range of +27.1 ± 3.6 to +38.1 ± 0.9 mV. Both oligonucleotide (ON) species bound strongly to Tat-peptide, forming stable complexes with loading efficiency of more than 86%. These complexes were relatively non cytotoxic as the cell viability of ∼90% was achieved. In conclusion, Tat-peptide has a great potential as siRNA and DsiRNA vector due to the formation of stable complexes with desirable physical characteristics, low toxicity and able to carry high amount of siRNA or DsiRNA.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage*
  7. Citartan M, Kaur H, Presela R, Tang TH
    Int J Pharm, 2019 Aug 15;567:118483.
    PMID: 31260780 DOI: 10.1016/j.ijpharm.2019.118483
    Aptamers, nucleic acid ligands that are specific against their corresponding targets are increasingly employed in a variety of applications including diagnostics and therapeutics. The specificity of the aptamers against their targets is also used as the basis for the formulation of the aptamer-based drug delivery system. In this review, we aim to provide an overview on the chaperoning roles of aptamers in acting as the cargo or load carriers, delivering contents to the targeted sites via cell surface receptors. Internalization of the aptamer-biomolecule conjugates via receptor-mediated endocytosis and the strategies to augment the rate of endocytosis are underscored. The cargos chaperoned by aptamers, ranging from siRNAs to DNA origami are illuminated. Possible impediments to the aptamer-based drug deliveries such as susceptibility to nuclease resistance, potentiality for immunogenicity activation, tumor heterogeneity are speculated and the corresponding amendment strategies to address these shortcomings are discussed. We prophesy that the future of the aptamer-based drug delivery will take a trajectory towards DNA nanorobot-based assay.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage
  8. Salama M, El-Desouky S, Alsayed A, El-Hussiny M, Magdy K, Fekry E, et al.
    Neurotox Res, 2019 May;35(4):987-992.
    PMID: 30362086 DOI: 10.1007/s12640-018-9974-3
    Tauopathy is a pathological hallmark of many neurodegenerative diseases. It is characterized by abnormal aggregates of pathological phosphotau and somatodendritic redistribution. One suggested strategy for treating tauopathy is to stimulate autophagy, hence, getting rid of these pathological protein aggregates. One key controller of autophagy is mTOR. Since stimulation of mTOR leads to inhibition of autophagy, inhibitors of mTOR will cause stimulation of autophagy process. In this report, tauopathy was induced in mice using annonacin. Blocking of mTOR was achieved through stereotaxic injection of siRNA against mTOR. The behavioral and immunohistochemical evaluation revealed the development of tauopathy model as proven by deterioration of behavioral performance in open field test and significant tau aggregates in annonacin-treated mice. Blocking of mTOR revealed significant clearance of tau aggregates in the injected side; however, tau expression was not affected by mTOR blockage.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage
  9. Abedini F, Hosseinkhani H, Ismail M, Domb AJ, Omar AR, Chong PP, et al.
    Int J Nanomedicine, 2012;7:4159-68.
    PMID: 22888250 DOI: 10.2147/IJN.S29823
    The failure of colorectal cancer treatments is partly due to overexpression of CXCR4 by tumor cells, which plays a critical role in cell metastasis. Moreover, serum alkaline phosphatase (ALP) levels are frequently elevated in patients with metastatic colorectal cancer. A polysaccharide, dextran, was chosen as the vector of siRNA. Spermine was conjugated to oxidized dextran by reductive amination process to obtain cationized dextran, so-called dextran-spermine, in order to prepare CXCR4-siRNAs/dextran-spermine nanoparticles. The fabricated nanoparticles were used in order to investigate whether downregulation of CXCR4 expression could affect serum ALP in mouse models of colorectal cancer.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage
  10. Lim MN, Lau NS, Chang KM, Leong CF, Zakaria Z
    Singapore Med J, 2007 Oct;48(10):932-8.
    PMID: 17909680
    The multidrug resistance gene, MDR1, is one of the genes responsible for resistance to chemotherapy in the treatment of leukaemia and other cancers. The discovery of RNA interference in mammalian cells has provided a powerful tool to inhibit the expression of this gene. However, very little is known about the transfection of leukaemia cells with short interfering RNA (siRNA) targeted at MDR1. This study aims to evaluate the effectiveness of two chemically-synthesised siRNA in modulating MDR1 gene and inhibiting P-glycoprotein expression in leukaemic cells. We also evaluated two siRNA delivery methods in this study.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage
  11. Hussain Z, Katas H, Yan SL, Jamaludin D
    Curr Drug Deliv, 2017;14(7):1016-1027.
    PMID: 28240178 DOI: 10.2174/1567201814666170224142446
    BACKGROUND: Despite having excellent anticancer efficacy and ability to knockdown gene expression, the therapeutic feasibility of Dicer-substrate small interfering RNA (DsiRNA) is limited due to its poor cellular uptake, chemical instability and rapid degradation in biological environments.

    OBJECTIVE: The present study was aimed to circumvent the pharmaceutical issues related to DsiRNA delivery to colon for the treatment of colorectal cancer.

    METHOD: In this study, we have prepared water-soluble chitosan (WSC)-DsiRNA complex nanoparticles (NPs) by a simple complexation method and subsequently coated with pectin to protect DsiRNA from gastric milieu.

    RESULTS: The mean particle size and zeta potential of the prepared WSC-DsiRNA complexes were varied from 145 ± 4 nm to 867 ± 81 nm and +38 ± 4 to -6.2 ± 2.7 mV respectively, when the concentrations of WSC (0.1%, 0.2% and 0.3% w/v) and pectin (0.1%, 0.2% and 0.25% w/v) were varied. The electron microscopic analysis revealed that morphology of WSC-DsiRNA complexes was varied from smooth spherical to irregular spherical. Cytotoxicity analysis demonstrated that viability of colorectal adenocarcinoma cell was decreased when the dose of WSC-DsiRNA was increased over the incubation from 24 to 48 h. A significantly low cumulative release of DsiRNA in simulated gastric (<15%) and intestinal fluids (<30%) and a marked increase in its release (>90%) in simulated colonic fluid (SCF) evidenced the feasibility and suitability of WSC-DsiRNA complexes for the colonic delivery.

    CONCLUSION: These findings clearly indicated promising potential of WSC-DsiRNA complexes as a carrier to delivery DsiRNA to colon for the treatment of colorectal cancer.

    Matched MeSH terms: RNA, Small Interfering/administration & dosage*
  12. Li YT, Chua MJ, Kunnath AP, Chowdhury EH
    Int J Nanomedicine, 2012;7:2473-81.
    PMID: 22701315 DOI: 10.2147/IJN.S30500
    Multidrug resistance, a major impediment to successful cancer chemotherapy, is the result of overexpression of ATP-binding cassette (ABC) transporters extruding internalized drugs. Silencing of ABC transporter gene expression with small interfering RNA (siRNA) could be an attractive approach to overcome multidrug resistance of cancer, although delivery of siRNA remains a major hurdle to fully exploit the potential of siRNA-based therapeutics. Recently, we have developed pH-sensitive carbonate apatite nanoparticles to efficiently carry and transport siRNA across the cell membrane, enabling knockdown of the cyclin B1 gene and consequential induction of apoptosis in synergy with anti-cancer drugs.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage*
  13. Tiash S, Chowdhury EH
    J Drug Target, 2019 03;27(3):325-337.
    PMID: 30221549 DOI: 10.1080/1061186X.2018.1525388
    Chemotherapy, the commonly favoured approach to treat cancer is frequently associated with treatment failure and recurrence of disease as a result of development of multidrug resistance (MDR) with concomitant over-expression of drug efflux proteins on cancer cells. One of the most widely used drugs, doxorubicin (Dox) is a substrate of three different ATP-binding cassette (ABC) transporters, namely, ABCB1, ABCG2 and ABCC1, predominantly contributing to MDR phenotype in cancer. To silence these transporter-coding genes and thus enhance the therapeutic efficacy of Dox, pH-sensitive carbonate apatite (CA) nanoparticles (NPs) were employed as a carrier system to co-deliver siRNAs against these genes and Dox in breast cancer cells and in a syngeneic breast cancer mouse model. siRNAs and Dox were complexed with NPs by incubation at 37 °C and used to treat cancer cell lines to check cell viability and caspase-mediated signal. 4T1 cells-induced breast cancer mouse model was used for treatment with the complex to confirm their action in tumour regression. Smaller (∼200 nm) and less polydisperse NPs that were taken up more effectively by tumour tissue could enhance Dox chemosensitivity, significantly reducing the tumour size in a very low dose of Dox (0.34 mg/kg), in contrast to the limited effect observed in breast cancer cell lines. The study thus proposes that simultaneous delivery of siRNAs against transporter genes and Dox with the help of CA NPs could be a potential therapeutic intervention in effectively treating MDR breast cancer.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage
  14. Tiash S, Chua MJ, Chowdhury EH
    Int J Oncol, 2016 Jun;48(6):2359-66.
    PMID: 27035628 DOI: 10.3892/ijo.2016.3452
    Treatment of breast cancer, the second leading cause of female deaths worldwide, with classical drugs is often accompanied by treatment failure and relapse of disease condition. Development of chemoresistance and drug toxicity compels compromising the drug concentration below the threshold level with the consequence of therapeutic inefficacy. Moreover, amplification and over-activation of proto-oncogenes in tumor cells make the treatment more challenging. The oncogene, ROS1 which is highly expressed in diverse types of cancers including breast carcinoma, functions as a survival protein aiding cancer progression. Thus we speculated that selective silencing of ROS1 gene by carrier-mediated delivery of siRNA might sensitize the cancer cells to the classical drugs at a relatively low concentration. In this investigation we showed that intracellular delivery of c-ROS1-targeting siRNA using pH-sensitive inorganic nanoparticles of carbonate apatite sensitizes mouse breast cancer cells (4T1) to doxorubicin, but not to cisplatin or paclitaxel, with the highest enhancement in chemosensitivity obtained at 40 nM of the drug concentration. Although intravenous administrations of ROS1-loaded nanoparticles reduced growth of the tumor, a further substantial effect on growth retardation was noted when the mice were treated with the siRNA- and Dox-bound particles, thus suggesting that silencing of ROS1 gene could sensitize the mouse breast cancer cells both in vitro and in vivo to doxorubicin as a result of synergistic effect of the gene knockdown and the drug action, eventually preventing activation of the survival pathway protein, AKT1. Our findings therefore provide valuable insight into the potential cross-talk between the pathways of ROS1 and doxorubicin for future development of effective therapeutics for breast cancer.
    Matched MeSH terms: RNA, Small Interfering/administration & dosage*
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