فهرست مطالب
Advanced Pharmaceutical Bulletin
Volume:11 Issue: 4, Sep 2021
- تاریخ انتشار: 1400/08/01
- تعداد عناوین: 21
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Pages 580-594
Cancer is a complex multifactorial process, unchecked and abrupt division, and cell growth— conventional chemotherapy, along with radiotherapy, is used to treat breast cancer. Due to reduce efficacy and less survival rate, there is a particular need for the discovery of new active anticancer agents. Natural resources such as terrestrial/marine plants or organisms are a promising source for the generation of new therapeutics with improving efficacy. The screening of natural plant extracts and fractions, isolations of phytochemicals, and mechanistic study of those potential compounds play a remarkable role in the development of new therapeutic drugs with increased efficacy. Cancer is a multistage disease with complex signaling cascades. The initial study of screening whole extracts or fractions and later the isolation of secondary compounds and their mechanism of action study gives a clue of potential therapeutic agents for future drug development. The phytochemicals present in extracts/fractions produce remarkable effects due to synergistically targeting multiple signals. In this review, the molecular targets of extracts/ fractions and isolated compounds highlighted. The therapeutic agent’s mechanistic targets in drug development focused involves; i) Induction of Apoptosis, ii) modulating cell cycle arrest, iii) Inhibition or suppression of invasion and metastasis and iv) various other prosurvival signaling pathways. The phytochemicals and their modified analogs identified as future potential candidates for anticancer chemotherapy
Keywords: Apoptosis, Breast cancer, Cell cycle arrest, Drug development, Natural products, Mechanism of action, Phytochemicals, Plant anticancer drugs -
Pages 595-600
The hypoxic environment is a substantial factor in maintenance, proliferation, and differentiation of the cell cultures. Low oxygen is known as a potent chondrogenesis stimulus in stem cells that is important for clinical application and engineering of functional cartilage. Hypoxia can potentially induce angiogenesis process by secretion of cytokines. This systematic review goal is to discover the effect of hypoxic condition on tendon/ ligament culture and the best oxygen level of hypoxia for in vitro and in vivo studies. We included 21 articles. A comprehensive review of this database confirms that the hypoxic condition is a substantial factor in the maintenance, proliferation, and differentiation of ligament/tendon cultures. Cell proliferation in the severe hypoxic (oxygen concentration of 1%) group at 24 hours post-cultivation was considered significant, but cell proliferation was markedly inhibited in the severe hypoxic group after 48 h.
Keywords: _ Hypoxic condition, Ligament, Tendon, Culture -
Pages 601-617
Traditional medicine is a comprehensive term for ancient, culture-bound health care practices that existed before the use of science in health matters and has been used for centuries. Medicinal plants are used to treat patients with cardiovascular diseases, which may occur due to ailments of the heart and blood vessels and comprise heart attacks, cerebrovascular diseases, hypertension, and heart failure. Hypertension causes difficulty in the functioning of the heart and is involved in atherosclerosis, raising the risk of heart attack and stroke. Many drugs are available for managing these diseases, though common antihypertensive drugs are generally accompanied by many side effects. Medicinal herbs have several active substances with pharmacological and prophylactic properties that can be used in the treatment of hypertension. This review presents an overview of some medicinal plants that have been shown to have hypotensive or antihypertensive properties.
Keywords: _ Traditional medicine, Hypertensionmanagement, Herbal medicine, Persian medicine, Cardiovascular diseases -
DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC TreatmentPages 618-623
Triple-negative breast cancer (TNBC) is the most aggressive and heterogeneous cancer subtypes. High rates of metastasis, poor prognosis, and drug resistance are the major problems associated with TNBC. The current chemotherapeutics eliminate only the bulk tumor cells (non-BCSCs) and do not affect breast cancer stem cells (BCSCs). The BCSCs which are left behind after chemotherapy is reported to promote recurrence and metastasis of TNBC. Death receptor-5 (DR-5) is exclusively expressed in TNBCs and mediates the extrinsic pathway of apoptosis. DR-5, therefore, can be exploited for targeted drug delivery and to induce apoptosis. Gammasecretase mediated Notch signaling in BCSCs regulates its proliferation, differentiation, and metastasis. The endogenous ligand, delta-like ligand 4 (DLL4), is reported to activate this Notch signaling in TNBC. Blocking this signaling pathway using both gamma-secretase inhibitors (GSIs) and DLL4 monoclonal antibody (mAb) may produce synergistic benefits. Further, the GSIs (DAPT, LY-411575, RO4929097, MK0752, etc.) suffer from poor bioavailability and off-target side effects such as diarrhea, suppression of lymphopoiesis, headache, hypertension, fatigue, and ventricular dysfunctions. In this hypothesis, we discuss solid lipid nanoparticles (SLNs) based drug delivery systems containing GSIs and surface modified with DR-5 and DLL4 monoclonal antibodies (mAb) to effectivity target and treat TNBC. The delivery system is designed to deliver the drug cargo precisely to TNBCs through its DR-5 receptors and hence expected to reduce the off-target side effects of GSIs. Further, DLL4 mAb and GSIs are expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis.
Keywords: Triple negative breast cancer(TNBC), Death receptor 5 (DR-5), Delta-like ligand 4 (DLL4), Notch Signaling, Gamma secretase inhibitors(GSIs), Dual targeting -
Pages 624-631Purpose
This paper established the application of synthesized graphitic carbon nitride nanosheets (GCNNs) as an influential dispersive solid phase extraction (DSPE) adsorbent in extracting methamphetamine from complicated urine media coupled with high performance liquid chromatography.
MethodsThe GCNNs were synthesized easily and applied as adsorbent in the extraction process. The effective extraction parameters were investigated by one-parameter-at-a-time. Under optimized conditions the method was validated.
ResultsThe calibration curve was plotted in the concentration range of 50-1500 ng/mL through the optimized conditions and the proposed method was validated. The method was used for the analysis of positive urine samples and showed satisfactory results with the average 99.7% relative recovery.
ConclusionThe results persuade the capability of this novel method in analyzing of the positive urine samples in diverse clinical and forensic laboratories.
Keywords: _ Graphitic carbon nitride, Dispersive solid phaseextraction, Methamphetamine, Urine -
Pages 632-642Purpose
Ranibizumab is a monoclonal antibody fragment, targeting all isoforms of vascular endothelial growth factor A (VEGF-A), a protein involved in angiogenesis. It is used to treat age-related macular degeneration (AMD), retinal vein occlusion, and diabetic macular edema, which are associated with blindness worldwide. However, proper treatment can decrease the loss of vision in about 90% of patients. Because of poor drug uptake in topical therapy and several adverse side effects of systemic irregularities and intravitreal injections, sustained-release drug delivery systems are more suitable for treatment. However, there are many challenges in the development of these systems due to the loss of protein activities.
MethodsAfter drug complexation by the ion pairing method and preparation of a polymeric implant, containing the drug, the characteristics of the complexes were examined by Fouriertransform infrared spectroscopy and circular dichroism spectroscopy. The stability of antibody activity and biocompatibility of the released drug from the implant were assessed by bioassays and MTT assay, respectively. Finally, the release kinetics were investigated.
ResultsThe bioassays showed the higher activity of the drug complex, compared to the free form, besides good biocompatibility in vitro. Also, the release data confirmed sustained and controlled release characteristics for the prepared implant.
ConclusionIn this study, for the first time, we proposed a method for developing a sustainedrelease intraocular implant, consisting of ranibizumab by the heating method. This method allows for the industrial production of ranibizumab by extrusion and eliminates the complications related to reservoir systems.
Keywords: _ Ranibizumab, Implant, VEGF-A, Extrusion method, Sustained release -
Pages 643-650Purpose
The ginger root extract has shown remarkable antimicrobial effects. Nanocarriers based on biodegradable polymers (like chitosan) are promising drug delivery vehicles for antibacterial compounds. In this study, aqueous and methanolic extracts of ginger root were prepared, loaded on chitosan nanoparticles (NPs), and their antimicrobial effects were investigated.
MethodsThe NPs were prepared using the ionic gelation technique. The central composite design model was employed to optimize the formulation variables and achieve the minimum particle size and maximum zeta potential. The total phenol content of the powdered extracts was determined. The antimicrobial activity of the NPs was evaluated by the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC).
ResultsThe optimum size of NPs containing methanolic or aqueous extract were 188.3 and 154.7 nm, with a zeta potential of 29.1 and 32.1 mv, and entrapment efficiency percent (E.E.%) of 61.57±3.12% and 44.26±2.57%, respectively. Transmission electronic microscopy images confirmed the spherical particles in the low nanometer range. The phenol content of methanol extract was higher than the aqueous one (60.216 ± 1.83 and 39.835 ± 1.72 mg gallic acid equivalent/100 g), respectively). According to the results of the MIC and MBC, methanol extract NPs showed more potent antimicrobial effects, which seems to be associated with higher concentrations of phenolic compounds. The FTIR spectrophotometry showed no chemical interaction between the extracts and other ingredients.
ConclusionThe results demonstrated that current NPs significantly increased the antibacterial effects of ginger extracts and could be selected for further evaluation.
Keywords: _ Ginger root extract, Chitosan, Nanoparticles, MIC, Drug delivery -
Pages 651-662Purpose
The present study focuses on a systemic approach to develop liposomal aztreonam as a promising dosage form for inhalation therapy in the treatment of pneumonia and explores the in-vitro antimicrobial and cell uptake efficacy.
MethodsLiposomes were prepared by ethanol injection method using the lipids - soya phosphatidylcholine (SP) and cholesterol (CH). A central composite design (CCD) was employed to optimize the lipid composition to evaluate the effect on vesicle size, zeta potential and entrapment efficiency of the formulation. A numerical and graphical optimization was carried out to predict the optimized blend. The optimized formulation was characterized for vesicle size, surface charge, encapsulation, surface morphology, differential scanning calorimetry (DSC), powder X Ray Diffraction (PXRD), thermogravimetric analysis (TGA), in vitro diffusion, accelerated stability studies, antimicrobial studies on Pseudomonas aeruginosa NCIM 2200 and in vitro cell uptake studies.
ResultsThe optimized formulation was found to have a particle size of 144 nm, a surface charge of -35 mV, with satisfactory drug entrapment. The surface morphology study proved the formation of nanosized vesicles. The drug release from liposomal matrix was biphasic in nature. The solid-state study revealed the reason for good encapsulation of drug. The moisture retention capacity was found to be minimum. The anti-microbial study revealed the potential antibacterial activity of the optimized formulation over the pure drug. The formulation was found to be safe on the epithelial cells and showed a marked increase in cellular uptake of aztreonam in a lipid carrier.
ConclusionIt can be concluded that the optimized liposomal aztreonam could be considered as a promising approach for the delivery of aztreonam through inhalation.
Keywords: Aztreonam, Liposomes, Statistical optimization, Antimicrobial study, Cell uptake study -
Pages 663-674Purpose
The Objective of the present investigation was to enhance the skin delivery of vitamin A (Vit A) via producing solid lipid nanoparticles (SLNs) through ultrasonication technique.
MethodsFor achieving optimal skin delivery, impacts of two surfactants ratio of Tween80:Span80 on nanoparticles (NPs) features and the respective functions were examined. Powder X-ray diffractometer (PXRD), photon correlation spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC) were applied for characterizing the solid state of Vit A in the SLN.
ResultsResults showed that size of the NPs is usually enhanced by adding co-emulsifier (Span80). Notably, minimum NPs size (64.85±4.259 nm) was achieved while the hydrophiliclipophilic balance (HLB) of the binary surfactants was 12.08, close to HLB of beeswax (HLB=12) as lipid matrix. Also, maximum entrapment efficiency (66.01±8.670%) was observed in the formulation. DSC thermogram indicated an amorphous form of Vit A in SLN. ATR-FTIR spectra of Vit A-SLN illustrated that prominent functional groups are found in the formulations that might be a sign of acceptable entrapment of Vit A in a lipid matrix. Moreover, ATR-FTIR studies showed no chemical interactions between Vit A and excipients. Skin irritation test proved the non-irritancy of Vit A-SLN2, when applied to the dorsal region of Wistar rats. Finally, any cellular toxicity was not seen for NPs.
ConclusionIt was found that the procured Vit A-SLNs could be utilized as potent carriers for the dermal delivery of Vit A.
Keywords: _ Vitamin A, Solid lipid nanoparticle, Dermal delivery, Skin irritation -
Pages 675-683Purpose
This study aimed to design gentamicin-conjugated poly (amidoamine) (PAMAM) dendrimers to increase the therapeutic efficiency of gentamicin against Pseudomonas aeruginosa.
MethodsGentamicin-presenting dendrimers were synthesized using MAL-PEG3400-NHS as a redox-sensitive linker to attach gentamicin to the surface of G4 PAMAM dendrimers. The gentamicin molecules were thiolated by using Traut reagent. Then, the functionalized gentamicin molecules were attached to PEGylated PAMAM dendrimers through simple and high selectively maleimide (MAL)-thiol reaction. The structure of gentamicin-conjugated PAMAM dendrimers was characterized and confirmed using nuclear magnetic resonance (NMR), dynamic light scattering (DLS), zeta potential analysis, and transmission electron microscopy (TEM) imaging. The antibacterial properties of the synthesized complex were examined on P. aeruginosa and compared to gentamycin alone.
ResultsNMR, DLS, zeta potential analysis, and TEM imaging revealed the successful conjugation of gentamicin to PAMAM dendrimers. Data showed the appropriate physicochemical properties of the synthesized nanoparticles. We found a 3-fold increase in the antibacterial properties of gentamicin conjugated to the surface of PAMAM dendrimers compared to non-conjugated gentamicin. Based on data, the anti-biofilm effects of PAMAM-Gentamicin dendrimers increased at least 13 times more than the gentamicin in normal conditions.
ConclusionData confirmed that PAMAM dendrimer harboring gentamicin could be touted as a novel smart drug delivery system in infectious conditions.
Keywords: Gentamicin, PAMAM dendrimers, Pseudomonas aeruginosa, Drug delivery, Anti-bacterial capacity -
Pages 684-692Purpose
Microbial biofilms are one of the main causes of persistent human infections. Encapsulation of an antibiotic and a biofilm dispersal agent within a nano-carrier has been recognized as a novel approach to combat the problem of biofilm-related infections. Here, we develop the nanoliposomal formulation for delivery of vancomycin in combination with cis-2- decenoic acid (C2DA), to Staphylococcus epidermidis biofilm. The effects of the formulations were studied at two stages: biofilm growth inhabitation and biofilm eradication.
MethodsLiposomal formulations were prepared by the solvent evaporation dehydrationrehydration method and were evaluated for size, zeta potential, and encapsulation efficacy. The ability of different agents in free and encapsulated forms were assessed to evaluate the anti-biofilm activities.
ResultsVancomycin and C2DA were successfully co-encapsulated in the same nanoliposome (liposomal combination). The zeta potential values of the liposomal formulations of vancomycin, C2DA, and the liposomal combination were 37.2, 40.2, 51.5 mV, and the mean sizes of these liposomal formulations were 167.8±1.5, 215.5±8.8, 235.5±0.01, respectively. Encapsulation efficacy of C2DA was 65% and about 40% for vancomycin. The results indicated that liposomal combination exerted strong anti-biofilm activities, slightly exceeding those observed by the free form of a combination of vancomycin and C2DA, but higher than either agent used alone in their free forms. The anti-biofilm activity of formulations followed concentration and time-dependent manner.
ConclusionThe combination of vancomycin and C2DA could inhibit biofilm formation. Employing the liposomal combination is a considerable method to remove bacterial biofilm.
Keywords: Liposome, Biofilm, Biofilm dispersion, Staphylococcus epidermidis, Vancomycin, Cis-2-decenoic acid -
Pages 693-699Purpose
The present study was performed to examine whether caspofungin-coated gold nanoparticles (CAS-AuNPs) may offer the right platform for sensitivity induction in resistant isolates.
MethodsA total of 58 archived Candida species were enrolled in the research. The identification of Candida spp. was performed using polymerase chain reaction-restriction fragment length polymorphism and HWP1 gene amplification approaches. The conjugated CAS-AuNPs were synthesized and then characterized using transmission electron microscopy (TEM) and Zetasizer system to determine their morphology, size, and charge. Furthermore, the efficacy was assessed based on the Clinical and Laboratory Standards Institute M60. Finally, the interaction of CASAuNPs with Candida element was evaluated via scanning electron microscopy (SEM).
ResultsAccording to the TEM results, the synthesized CAS-AuNPs had a spherical shape with an average size of 20 nm. The Zeta potential of CAS-AuNPs was -38.2 mV. Statistical analyses showed that CAS-AuNPs could significantly reduce the minimum inhibitory concentration against C. albicans (P=0.0005) and non-albicans Candida (NAC) species (P<0.0001). All isolates had a MIC value of ≥ 4 µg/ml for CAS, except for C. glabrata. The results of SEM analysis confirmed the effects of AuNPs on the cell wall structure of C. globrata with the formation of pores.
ConclusionAccording to findings, CAS-AuNPs conjugates had significant antifungal effects against Candida spp. Therefore, it can be concluded that the encapsulation of antifungal drugs in combination with NPs not only diminishes side effects but also enhances the effectiveness of the medications.
Keywords: _ Candida albicans, Non-albicans Candida, CAS-AuNPs conjugate, Caspofungin -
Pages 700-711Purpose
The aminoadamantane derivative of L-histidyl-1-adamantayl ethylamine hydrochloride (HCl*H-His-Rim) has showed a high inhibition level against influenza A virus strains in vitro. The aim of this work is to search and establish evidence of the direct effect of the drug on influenza A virus proton channel M2.
MethodsThe compound HCl*H-His-Rim was obtained by classical peptide synthesis methods. Influenza A virus mutants of A/PuertoRico/8/34(H1N1) strain were obtained by reverse genetics methods. The mutant samples of the virus were cultured on chicken embryos with a virus titer in the hemagglutination test. ELISA was carried out on Madin-Darby canine kidney (MDCK) monolayer cells when multiplying the virus 10-4-10-6. The binding stability of HCl*H-His-Rim was compared to those of M2 (S31N) and M2 (S31N_A30T) channels by molecular dynamic (MD) modeling. The calculation was performed taking into account the interaction with the model lipid bilayer (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) in the presence of water molecules in accordance with the three-center model.
ResultsIt was found that HCl*H-His-Rim is a direct action drug against influenza A. The most likely conformation of drug binding to target protein has been shown. It has been found that the A30T mutation reduces the binding energy of the drug, and the results obtained in vitro have confirmed the data calculated in silico.
ConclusionThe mechanism of action of HCl*H-His-Rim is directly related to the suppression of the function of the proton channel M2 of influenza A virus.
Keywords: Antiviral, Drug resistance, Influenza virus, M2 proton channel, Molecular docking, Reverse genetics -
Pages 712-718Purpose
Previous studies have documented that cumulus granulosa cells (GCs) can transdifferentiation into different non-ovarian cells, showing their multipotentiality to repopulate the injured cells in ovarian tissue. The current experiment is aimed to assess the differentiation capacity of human cumulus GCs toward the oocyte-like phenotype in vitro.
MethodsGCs were isolated from healthy female volunteers subjected to in vitro fertilization or intra-cytoplasmic sperm injection (IVF-ICSI). The effect of different media supplemented with leukemia inhibitory factors (LIFs), 5 ng/mL estradiol, and 0.005 IU/mL follicle-stimulating hormone (FSH) were investigated to the differentiation of GCs toward oocyte-like phenotype via monitoring the expression of Oct3/4 and GATA-4 using flow cytometry analysis. The expression of genes such as FIGLA, NOBOX, and SYCP3 was measured by real-time polymerase chain reaction (PCR) assay. We also assess morphological adaptation by using bright-field microscopic imaging.
ResultsExposure of GCs to LIFs increased the number of cells expressing stemness factor Oct3/4 coincided with the suppression of GATA-4 after 7 days (P<0.05). We found that the transcript level of all genes FIGLA, Nobox, and SYCP-3 decreased in cells after treatment with a FSH (P<0.05). According to our data, the incubation of GCs with estradiol increased the expression of genes related to the oocyte-like phenotype.
ConclusionOur finding revealed that the combination of LIFs and estradiol could induce the GCs’ oogenesis capacity and thereby is p
Keywords: Granulosa cells, Leukemia inhibitory factors, Follicle-stimulating hormone, Estradiol, Oocyte-like cells -
Pages 719-727Purpose
Myocardial infarction (MI), known as a multifactorial disease, remains the predominant cause of mortality and sudden deaths annually. The current study aimed to measure the expression of microRNA-1 and microRNA-221-3p in MI patients.
MethodsIn the current study, 100 healthy controls (with no history of heart disease) and 200 patients with MI were selected. Patients were divided into two groups based on angiography
resultsnormal (no significant artery stenosis) and primary percutaneous coronary intervention (primary PCI, significant artery stenosis). The levels of microRNA-1 and microRNA-221-3p were quantified using real-time quantitative polymerase chain reaction. The correlation between levels of microRNAs and the common cardiac markers were analyzed statistically.
ResultsIn comparison to fold change, microRNA-1 elevations were 8.5-fold in normal patients and 60-fold in patients with primary PCI; while microRNA-221-3p levels were 210- fold higher in primary PCI and 31.31-fold higher in normal cases compared with the healthy controls. Receiver operating characteristic analysis showed that the area under the curve (AUC) for circulating microRNA-1 and microRNA-221 were 0.903 and 0.958 in normal patients and 0.927 and 0.985 in primary PCI patients (p <0.0001), respectively. Pearson correlation (ρ) analysis showed that circulation of microRNA-1 correlated with serum levels of cardiac troponin I (CTnI) (ρ=0.24), creatinine (ρ =0.34), creatinine kinase-myocardial band (CK-MB) (ρ=0.31), and microRNA-221-3p was significantly correlated with serum levels of CTnI (ρ =0.6), creatinine (ρ=0.41), and CK-MB (ρ=0.37), (P <0.0001).
ConclusionThe study underscored the potential of microRNA-1 and microRNA-221-3p as informative biomarkers and positively correlated with artery stenosis in MI.
Keywords: MicroRNA-1, MicroRNA-221-3p, Myocardial Infarction, Artery stenosis -
Pages 728-738Purpose
This study focuses on the effect of length and structure of attached polyethylene glycol (PEG) chain on hydrodynamic radius (Rh ) and chromatographic retention of PEGylated protein. To this aim human serum albumin (HSA) as a standard protein was PEGylated site specifically with mPEG-maleimide.
MethodsSeparated PEG_HSA fractions were analyzed by size exclusion and anion exchange chromatography (AExC). The purity of fractions and the relative mobility of PEGylated and native proteins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Hydrodynamic radius was determined based on the retention time of fractions on size exclusion chromatography (SEC), and also according to the previously reported equations.
ResultsA linear relation was shown between the molecular weight of attached PEG and Rh of PEGylated HSA. No significant difference between Rh of proteins modified with linear and branched PEG was shown. In SDS-PAGE, the delaying effect of branched PEG on movement of PEGylated protein was higher than that of linear PEG.
ConclusionAs PEGylated HSA and dimer HSA have almost the same size and in SEC they elute at very close retention times, so in this case ion exchange chromatography (IExC) is more effective than SEC in separation of PEGylated HSA. Branched PEG- HSA showed earlier elution on anion exchange chromatography compared to linear PEG-HSA, that this can explain the different shielding effect of various structures of attached PEGs. The smaller size of PEGylated HSA in compare to the sum of the hydrodynamic radiuses of native HSA and attached PEG could be as a result of shielded attachment of polymer around protein.
Keywords: Human serum albumin, Ion-exchange chromatography, PEG-HSA, PEGylation, PEGylated, Size exclusion chromatography -
Pages 739-745Purpose
Mesenchymal stem cells (MSCs) have immunomodulatory traits making them a promising choice in the treatment of inflammatory diseases such as graft-versus-host disease (GVHD). Tumor necrosis factor-alpha (TNFα) is a major player of inflammatory disease which is blocked by infliximab to reduce the inflammation. The present study aims to assess the infliximab effects on the anti-inflammatory properties of MSCs.
MethodsIn this study, bone marrow mesenchymal stem cells (BMMSCs) were co-cultured with peripheral blood mononuclear cells (PBMCs) of GVHD patients in the presence of 10, 20 and 30 µg/mL of infliximab for 48 and 72 hours. The mRNA expression of indoleamine-2,3- dioxygenase (IDO) and inducible nitric oxide synthase (iNOS), as well as the secreted amount of prostaglandin E2 (PGE2) in the culture supernatant, were examined.
ResultsThe results of this study show that the expression of IDO and iNOS genes, as well as the secretion amount of PGE2 in co-cultured groups raised dramatically, compared to the culture of BMMSCs or PBMCs alone. In co-culture groups containing infliximab, the expression of IDO and iNOS and also the amount of released PGE2 was significantly decreased compared to the control group without infliximab. However, no difference was found in the expression of assayed factors between 48 and 72 hours of treatments.
ConclusionAs an anti-TNFα agent, infliximab can decrease the inflammation in the microenvironment of MSCs, which might mitigate the immunomodulatory effects of MSCs. These effects of anti-inflammatory agents on the immunomodulatory capacity of MSCs should be considered in MSC therapy
Keywords: _ Mesenchymal stem cells, Infliximab, Immunomodulation, Tumor necrosis factor -
Pages 746-754Purpose
Cisplatin is a cancer chemotherapeutic drug that has been extensively used in the treatment of a variety of cancers. However, the full usage of cisplatin is limited due to its treatment associated development of multiple side effects in the host. In the present study, the modulatory effect of rutin, a type of flavonoid, on the cisplatin mediated antitumor activity and allied genotoxicity in ascites Dalton’s lymphoma (DL)-bearing mice were investigated.
MethodsThe antitumor activity was determined by calculating the percent increase in the life span of mice, cell viability and scanning electron microscopy (SEM) of DL cells. Further, the modulatory effect of rutin on the cisplatin-induced genotoxic effects in the same DLbearing mice was assessed by the analysis of micronuclei, chromosomal aberration and sperm abnormality.
ResultsThe combination treatment of mice with rutin and cisplatin showed a considerable increase in the life span of the DL-bearing mice depicting better antitumor efficacy. SEM of these DL cells showed severe membrane deformities in DL cells such as fusion of cell membrane, membrane blebbing, cell shrinkage, membrane folding and loss in microvilli from the tumor cell surface which may lead to cell death. Cisplatin alone treatment caused an increase in the frequency of chromosomal aberrations, micronuclei and sperms abnormality. However, the combination treatment of DL-bearing mice with rutin and cisplatin comparatively reduced these genotoxic effects.
ConclusionThe overall findings suggest that rutin enhances the cisplatin-mediated antitumor activity and cytotoxicity against DL cells and at the same time diminishes the genotoxic effects induced by cisplatin in the DL-bearing mice.
Keywords: _ Rutin, Cisplatin, Dalton’s lymphoma, Antitumor activity, Genotoxicity -
Pages 755-764Purpose
The expression of miR-146a-5p and miR-193a-5p in colorectal cancer (CRC) is associated with cancer development, metastasis, and reduced survival rate of the tumor-suffered subjects. This examination aimed to assess the impact of these microRNAs (miRNAs) in CRC and their mechanisms in the proliferation and migration of cancer cells.
MethodsmiR-146a-5p and -193a-5p were transfected into the HT-29 cell line and assessed their impact on metastasis-related genes. The synergistic effects of these miRNAs on migration were evaluated by wound healing approach. To assess the influence of these miRNAs on the proliferation of and apoptosis of cells, the MTT test, annexin V staining test, and DAPI staining test were done. Then, the protein expression of extracellular-signal-regulated kinase (ERK) and phosphorylated ERK (p-ERK) were investigated.
ResultsmiR-146a-5p and-193a-5p could inhibit the CRC cells proliferation, and could synergistically induce apoptosis in CRC cells, and also repressed cell migration, and could reduce p-ERK expression.
ConclusionmiR-146a-5p and-193a-5p have an important role in cell viability and proliferation via ERK signaling pathway. Thus, the simultaneous use of these miRNAs may be suggested as a probable therapeutic strategy in this cancer therapy.
Keywords: miRNA-146a-5p, miRNA-193a-5p, Colorectal cancer, ERK pathway, Cell growth -
Pages 765-771Purpose
Conjugating cisplatin into hybrid nanoparticles is intended to enhance tumor accumulation in cancer therapy due to drug interaction with polymer and prevent premature drug release because of the presence of a lipid layer.
MethodsHybrid nanoparticles composed of polyethylene oxide-b-polymethacrylic acid, egg phosphatidylcholine, and surfactant, i.e. sodium cholate/sodium deoxycholate/Tween 80, were prepared by the injection method. Cisplatin was subsequently loaded by incubating the polymer-drug mixtures at the molar ratio of carboxylate ions of 2:1.
ResultsThe results showed that the addition of surfactants produced particle sizes between 33 and 52 nm. The addition of cisplatin increased the ζ-potential to slightly positive charges with encapsulation efficiencies of 5%-18%. An in vivo biodistribution study of mice identified a cisplatin plasma concentration of sodium cholate-modified hybrid nanoparticles 10 times higher than cisplatin solution, thus producing high tumor accumulation.
ConclusionConjugating cisp
Keywords: Cisplatin, Cancer, Egg phosphatifylcholine, Hybrid nanoparticles, Polyethylene oxide-bpolymethacrylic acid, Surfactants -
Pages 772-776Purpose
Novel cocrystals of nevirapine (NP) were designed and prepared with salicylamide and 3-hydroxy benzoic acid (3-HBA).
MethodsThe cocrystals were prepared by solvent drop grinding method by adding few drops of acetone to enhance the solubility and dissolution. The drug and cocrystals were characterized by differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD). The solubility of NP, its wet ground form, and cocrystals were investigated at different pH. Moreover, the effect of surfactant on solubility of cocrystals was also studied. Finally, intrinsic dissolution rate (IDR) and stability of cocrystals was examined.
ResultsThe characterization of cocrystals by DSC and PXRD revealed formation of new solid forms due to changes in thermogram and PXRD pattern. The cocrystal of NP with 3-HBA showed 4.5 folds greater solubility in pH 1.2 buffer and 5.5 folds in 1% Tween 80 as compared to original drug. IDR of cocrystals was higher than the pure drug in 0.1 N hydrochloric acid (HCl). Moreover, cocrystals were found physically stable after 3 months as evident from unchanged IDR.
ConclusionHence, the present research indicates the new stable solid forms of NP with improved dissolution rate than pure drug.
Keywords: Cocrysta, Nevirapine, Surfactant, pH, Dissolution