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1.
Int J Pharm X ; 6: 100214, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38024450

ABSTRACT

Combination therapy represents a promising strategy in cancer management by reducing chemotherapy resistance and associated side effects. Silymarin (SLM) has been extensively investigated due to its potent antioxidant properties and demonstrated efficacy against cancer cells. Under certain conditions however, polyphenolic compounds may also exhibit prooxidant activity by elevating intracellular reactive oxygen species (ROS), which can harm the target cells. In this study, we hypothesized that the simultaneous administration of iron (Fe) could alter the antioxidant characteristic of SLM nanoliposomes (SLM Lip) to a prooxidant state. Hence, we first developed a SLM Lip preparation using lipid film method, and then investigated the anti-oxidant properties as well as the cytotoxicity of the liposomal preparation. We also explored the efficacy of concomitant administration of iron sucrose and SML Lip on the tumor growth and survival of mice bearing tumors. We observed that exposing cells to iron, and consecutive treatment with SLM Lip (Fe + SLM Lip) could induce greater toxicity to 4 T1 breast cancer cells compared to SLM Lip. Further, Fe + SLM Lip combination demonstrated a time-dependent effect on reducing the catalase activity compared to SLM Lip, while iron treatment did not alter cell toxicity and catalase activity. In a mouse breast cancer model, the therapeutic efficacy of Fe + SLM Lip was superior compared to SLM Lip, and the treated animals survived longer. The histopathological findings did not reveal a significant damage to the major organs, whereas the most significant tumor necrosis was evident with Fe + SLM Lip treatment. The outcomes of the present investigation unequivocally underscored the prospective use of Fe + SLM combination in the context of cancer therapy, which warrants further scrutiny.

2.
Biochem Biophys Res Commun ; 676: 103-108, 2023 10 08.
Article in English | MEDLINE | ID: mdl-37506470

ABSTRACT

BACKGROUND: Acetaminophen (Act) overdose is a known inducer of liver failure in both children and adults. Cell annihilation ensues following acetaminophen overdose and its toxic metabolites by depleting cellular GSH storage and increasing ROS levels. Silymarin extract and its major compound silibinin (SLB) possess robust antioxidant properties by inducing ROS elimination; however, low bioavailability and rapid metabolism limit their applications. Herein, we aimed at using SLB liposomes to combat acetaminophen-induced acute liver toxicity. METHODS: We have developed a SLB-lipid complex to improve SLB loading efficiency within nanoliposome by using the lipid film method. Liposomes were characterized by using DLS and TEM analysis, and the release pattern, and toxicity profile on the normal cells as well as histopathological and serum analysis were investigated to reveal relevant enzyme activities in an animal model. RESULTS: Data demonstrated that negatively-charged SLB liposomes of 115 nm had homogeneous spherical morphology, and entrapped a considerable quantity of SLB of almost 40%. Liposomes shows a favorable release pattern and were not toxic against NIH3T3 mouse fibroblast cells. The animal study revealed that treatment of mice with SLB nanoliposomes could significantly preserve liver function as revealed by the reduced levels of ALT and AST hepatic enzymes as well as ALP in the serum. Our data indicated that intraperitoneal administration of SLB Lip could significantly reduce ALT enzyme levels (p < 0.05) compared to N-acetylcysteine, while i.v administration resulted in no significant difference compared to control animals with no treatment. CONCLUSION: The results of this study support the significant hepatoprotective effect of SLB nanoliposomes against acetaminophen-induced toxicity depending on the route of administration.


Subject(s)
Chemical and Drug Induced Liver Injury , Liver Failure , Mice , Animals , Silybin/pharmacology , Acetaminophen/pharmacology , Liposomes/metabolism , NIH 3T3 Cells , Reactive Oxygen Species/metabolism , Liver/metabolism , Liver Failure/pathology , Lipids/pharmacology , Chemical and Drug Induced Liver Injury/pathology
3.
Drug Discov Today ; 28(8): 103663, 2023 08.
Article in English | MEDLINE | ID: mdl-37315763

ABSTRACT

The novel coronavirus crisis caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was a global pandemic. Although various therapeutic approaches were developed over the past 2 years, novel strategies with more efficient applicability are required to target new variants. Aptamers are single-stranded (ss)RNA or DNA oligonucleotides capable of folding into unique 3D structures with robust binding affinity to a wide variety of targets following structural recognition. Aptamer-based theranostics have proven excellent capability for diagnosing and treating various viral infections. Herein, we review the current status and future perspective of the potential of aptamers as COVID-19 therapies.


Subject(s)
Aptamers, Nucleotide , COVID-19 , Humans , SARS-CoV-2 , Oligonucleotides/chemistry , DNA , RNA , Aptamers, Nucleotide/therapeutic use , Aptamers, Nucleotide/chemistry
4.
IET Nanobiotechnol ; 16(3): 67-77, 2022 May.
Article in English | MEDLINE | ID: mdl-35274474

ABSTRACT

After the outbreak of coronavirus disease 2019 (COVID-19) in December 2019 and the increasing number of SARS-CoV-2 infections all over the world, researchers are struggling to investigate effective therapeutic strategies for the treatment of this infection. Targeting viral small molecules that are involved in the process of infection is a promising strategy. Since many host factors are also used by SARS-CoV-2 during various stages of infection, down-regulating or silencing these factors can serve as an effective therapeutic tool. Several nucleic acid-based technologies including short interfering RNAs, antisense oligonucleotides, aptamers, DNAzymes, and ribozymes have been suggested for the control of SARS-CoV-2 as well as other respiratory viruses. The antisense technology also plays an indispensable role in the treatment of many other diseases including cancer, influenza, and acquired immunodeficiency syndrome. In this review, we summarised the potential applications of antisense technology for the treatment of coronaviruses and specifically COVID-19 infection.


Subject(s)
COVID-19 , COVID-19/therapy , Humans , SARS-CoV-2/genetics , Technology
5.
Infect Disord Drug Targets ; 22(1): e220321192415, 2022.
Article in English | MEDLINE | ID: mdl-33749564

ABSTRACT

In late 2019, a report from China was published stating a disease with an unknown cause. After that, the outbreak of the COVID-19 caused a pandemic in the world. On March 11, 2020, the outbreak of this virus was reported in 100 countries. The virus is currently spreading rapidly around the world. In the past, coronaviruses caused lifethreatening diseases such as SARS and MERS in some areas of the world. Although there is still a debate about the origin of this new coronavirus, it is most likely linked with some animals, including bats, civet, and pangolin. In this review, we try to describe the features of the new coronavirus as well as the recent diagnostic and therapeutic findings.


Subject(s)
COVID-19 , Chiroptera , Middle East Respiratory Syndrome Coronavirus , Animals , COVID-19/epidemiology , Humans , Pandemics , Prevalence , SARS-CoV-2
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