Candesartan Research Articles

Enhanced SIA-chemiluminescence probes for angiotensin II receptor antagonist detection using silver and gold nanoparticles: applications in pharmaceutical formulations

The present work describes three different sequential injection chemiluminescence systems for the detection of some angiotensin II receptor antagonists, such as candesartan cilexetil, valsartan and telmisartan.

Evaluation of the Discriminatory Power of USP Dissolution Method for Candesartan Cilexetil Tablets through Testing of Marketed Products in Egypt

Evaluation of the Discriminatory Power of USP Dissolution Method for Candesartan Cilexetil Tablets through Testing of Marketed Products in Egypt

HPMCAS as an effective precipitation inhibitor in amorphous solid dispersions of the poorly soluble drug candesartan cilexetil

Among the strategies to improve the biopharmaceutic properties of poorly soluble drugs, Supersaturating Drug Delivery Systems like polymer-based amorphous solid dispersions (SD) have been successfully applied. The screening of appropriate polymeric carriers to compose SD is a crucial point on their development. In this study, hydroxypropylmethylcellulose (HPMC), hydroxypropylmethylcellulose acetate succinate (HPMCAS) types L, M and H and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL) were evaluated by in vitro supersaturation studies regarding their anti-precipitant ability on the poorly soluble drug candesartan cilexetil (CC) under two different media, including biorelevant conditions. According to the results, HPMCAS M was considered the best carrier to develop SD containing CC among all the polymers tested, due to its good anti-precipitant performance in both media. In addition, the medium used in the in vitro supersaturation studies played an important role on the results, and its selection should be carefully done.

Stability-Indicating Liquid Chromatographic Methods with Photodiode Array Detection and Light Scattering Detection for Simultaneous Determination of Candesartan and Hydrochlorothiazide.

Development, validation and comparison of two stability-indicating LC methods, one with photodiode array detector (DAD) and the other with evaporative light scattering detector (ELSD), were performed for simultaneous determination of candesartan cilexetil (CANC) and hydrochlorothiazide (HCTZ), in pharmaceutical samples. A RP-18 column (125 mm × 4 mm, 5 μm) was used for separation of CANC, HCTZ and its major degradation products, using acetonitrile and phosphate buffer (pH 6.0) for DAD method and acetonitrile and water with acetic acid and triethylamine (pH 4.1) for ELSD method, as mobile phase in a gradient mode. The response with ELSD was fitted to a power function and the DAD response by a linear model over a range of 32-160 μg/mL for CANC and 25-125 μg/mL for HCTZ. The precision and accuracy of the methods were similar, with RSD below 3.0% and recovery between 98.1% and 103.9%. The drugs were subjected to stress conditions of hydrolysis, oxidation, photolysis, humidity and temperature. The degradation products were satisfactory separated from the main peaks and from each other. Both drugs mainly degrade by hydrolysis, showing the formation of one degradation product for HCTZ and two for CANC; its identification was conducted by LC/MS/MS. The methods were successfully applied to the analysis of CANC and HCTZ in combined commercial tablets. The performance of DAD and ELSD methods are comparable, therefore both methods are suitable for stability study and determination of CANC and HCTZ in pharmaceutical samples.

Effect of surfactants and hydrophilic polymers on the stability of an antihypertensive drug candesartan cilexetil: Evaluation by HPLC

The objective of this study is to investigate the effect of surfactants (polysorbate 80 and sodium lauryl sulphate) and hydrophilic polymers (polyvinylpyrrolidone and polyethylene glycol 6000) on the stability of candesartan cilexetil under isothermal stress conditions (100°C, 48h). HPLC method was employed to evaluate the drug content and formation of degradation products in stress samples. Drug and degradation products were separated on Hypersil BDS C18 (250×4.6mm, 5μ) column using acetonitrile-water (pH 2.8) in the ratio of 85:15% v/v as a mobile phase. Similar degradation behaviour of drug was observed with polyvinylpyrrolidone, polyethylene glycol 6000 and polysorbate 80; four common degradation peaks were observed at the retention time of 3.7, 4.5, 7.8 and 11minutes. One extra common degradation peak of very low intensity was also observed with polyethylene glycol 6000 and polysorbate 80 at the retention time of 4.2min. The drug was eluting at the retention time of 5.4min. In the case of sodium lauryl sulphate, two prominent degradation peaks were observed at the retention time of 3.7 and 13.25min along with few very low-intensity degradation peaks. The drug showed 41%, 64%, 72% and 98% degradation in presence of polyvinylpyrrolidone, polyethylene glycol 6000, polysorbate 80 and sodium lauryl sulphate, respectively.

Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study.

BackgroundAnthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change in circulating cardiovascular biomarkers, (2) the effect of metoprolol succinate and candesartan cilexetil on the biomarker response, and (3) the associations between on‐treatment changes in biomarker concentrations and subsequent left ventricular dysfunction in patients with early breast cancer receiving anthracyclines.Methods and ResultsThis report encompasses 121 women included in the 2×2 factorial, placebo‐controlled, double‐blind PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial with metoprolol and candesartan given concomitantly with anticancer therapy containing the anthracycline, epirubicin (total cumulative dose, 240–400 mg/m2). Cardiovascular magnetic resonance, echocardiography images, and circulating levels of biomarkers were obtained before and after anthracycline treatment. Cardiac troponins I and T, B‐type natriuretic peptide, N‐terminal pro‐B‐type natriuretic peptide, C‐reactive protein, and galectin‐3 increased during anthracycline therapy (all P<0.05). The troponin response was attenuated by metoprolol (P<0.05), but not candesartan. There was no association between change in biomarker concentrations and change in cardiac function during anthracycline therapy.ConclusionsTreatment with contemporary anthracycline doses for early breast cancer is associated with increase in circulating cardiovascular biomarkers. This increase is, however, not associated with early decline in ventricular function. Beta‐blockade may attenuate early myocardial injury, but whether this attenuation translates into reduced risk of developing ventricular dysfunction in the long term remains unclear.Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01434134.

Formulation and Optimization of Candesartan Cilexetil Nano Lipid Carrier: In Vitro and In Vivo Evaluation.

The objective of this study was to formulate and optimize Candesartan Cilexetil (CC) loaded nanostructured lipid carriers (NLCs) for enhanced oral bioavailability. Glycerol monostearate (GMS), Oleic acid, Tween 80 and Span 40 were selected as a solid lipid, liquid lipid, surfactant and co- surfactant, respectively. The CC-NLCs were prepared by hot emulsion probe sonication technique and optimized using experimental design approach. The formulated CC-NLCs were evaluated for various physicochemical parameters and further optimized formulation (CC-NLC-Opt) was assessed for in vivo pharmacokinetic and pharmacodynamic activity. The optimized formulation (CC-NLC-Opt) showed particle size (183.5±5.89nm), PDI (0.228±0.13), zeta potential (-28.2±0.99mV), and entrapment efficiency (88.9±3.69%). The comparative in vitro release study revealed that CC-NLC-Opt showed significantly better (p<0.05) release and enhanced permeation as compared to CC-suspension. The in vivo pharmacokinetic study gave many folds increase in oral bioavailability than CC suspension, which was further confirmed by antihypertensive activity in a murine model. Thus, the results of ex vivo permeation, pharmacokinetic study and pharmacodynamics study suggest the potential of CC-NLCs for improved oral delivery.

Nano-Hydroxyapatite-Derived Drug and Gene Co-Delivery System for Anti-Angiogenesis Therapy of Breast Cancer.

BackgroundBreast cancer is among the deadliest cancers across the world and is responsible for countless deaths. There is an urgent need for co-delivery systems which can simultaneously transport both drug and gene into a single cancer cell with low toxicity and high anti-angiogenesis efficiency.Material/MethodsIn the present study, well-formed amine-functionalized hydroxyapatite nanoparticles based on combined angiogenesis therapy for breast cancer were successfully constructed for the simultaneous delivery of p53 and candesartan (CD) (p53/CD/NHAP).ResultsIn vitro and in vivo experiments revealed that p53/CD/NHAP can effectively transfer the p53 gene and deliver the loaded CD to achieve preferable anti-breast cancer effect both at the cellular level and in tumor-bearing mice. This may possibly be due to the combined anti-angiogenic mechanisms of p53 and CD via different pathways.Conclusionsp53/CD/NHAP might be a candidate carrier for efficient anti-angiogenesis therapy of breast cancer.

Development of Pulsatile Drug Delivery for Chronotherapeutics of Hypertension

The goal of present work was to investigate the effects of rupturable material ethyl cellulose combines with erodible material Klucel EXF on the pulsatile release pattern of Candesartan cilexetil in order to prevent morning rise in blood pressure. A tablet prepared by compression coating method contains core and coat components. Core consists of active ingredients with its various superdisintegrants where as coat contains different grades of ethyl cellulose and Klucel HXF in various combinations. All these tablets were evaluated for its micromeritics, weight variations, hardness, friability and in vitro dissolution testing. Drug-excipients interactions were carried out by FTIR. Dissolution studies were carried out in simulated gastric fluid followed by phosphate buffer of pH 6.5. The optimized formulation PT6 which give lag time of 6 hrs and released 99.10 % within 7 hr, as well as found to be stable in ICH stability testing guidelines.

Thermal Behaviour of Candesartan Active substance and in pharmaceutical compounds

Thermal analysis is one of the most frequently used instrumental techniques in the pharmaceutical research, for the thermal characterization of different materials from solids to semi-solids, which are of pharmaceutical relevance. In this paper, simultaneous thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC) were used for characterization of the thermal behaviour of candesartan cilexetil � active substance (C-AS) under dynamic nitrogen atmosphere and nonisothermal conditions, in comparison with pharmaceutical product containing the corresponding active substance. It was observed that the commercial samples showed a different thermal profile than the standard sample, caused by the presence of excipients in the pharmaceutical product and to possible interaction of these with the active substance. The Fourier transformed infrared spectroscopy (FT-IR) and X-ray powder diffraction (XRPD) were used as complementary techniques adequately implement and assist in interpretation of the thermal results. The main conclusion of this comparative study was that the TG/DTG and DSC curves, together with the FT-IR spectra, respectively X-ray difractograms constitute believe data for the discrimination between the pure substance and pharmaceutical forms.

A REVIEW ON GOLD NANOPRTICLES SYNTHESIS AND CHARACTERIZATION

Gold nano particles (GNP) have exceptional biocompatibility and possess unique structural, electronic, magnetic, optical, catalytic and molecular recognition properties. Hence GNPs are very attractive for many biological applications. Being noble metal, the GNPs are resistant to oxide formation. Their electronic, magnetic and optical properties are size dependent. The optical properties of gold nano particles depend on nano particles size, shape, aggregation state, and local environment and are tuneable throughout the visible and near-infrared region. The current paper gives a brief review of different methods of synthesis of GNP with uniform size and shape and characterization of GNP by UV spectroscopy, dynamic light scattering, scanning electron microscopy and Fourier transform Infra Red spectroscopy along with applications of GNPs. Peer Review History: Received 1 July 2017; Revised 5 August; Accepted 2 September, Available online 15 September 2017 Academic Editor: Dr. Ali Abdullah Al-yahawi, Al-Razi university, Department of Pharmacy, Yemen, alyahawipharm@yahoo.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Dr. Sally A. El-Zahaby, Pharos University in Alexandria, Egypt, sally.elzahaby@yahoo.com Dr. Maha Khalifa Ahmed Khalifa, Al-Azhar Universit - Cairo, Egypt, mahakhalifa.ahmed@hotmail.com Similar Articles: SCREENING STUDY FOR FORMULATION VARIABLES IN PREPARATION AND CHARACTERIZATION OF CANDESARTAN CILEXETIL LOADED NANOSTRUCTURED LIPID CARRIERS

Development and in vitro/in vivo performance of self-nanoemulsifying drug delivery systems loaded with candesartan cilexetil

Candesartan cilexetil is widely used in the management of hypertension and heart failure. The drug delivery encounters obstacles of poor aqueous solubility, efflux by intestinal P-glycoprotein and vulnerability to enzymatic degradation in small intestine. Self-nanoemulsifying drug delivery systems (SNEDDS) loaded with candesartan cilexetil were successfully developed to overcome such obstacles. Preliminary screening was carried out to select proper surfactant, co-surfactant and oil combination for successful SNEDDS formulation. All screened excipients were reported for their P-glycoprotein and cytochrome P450 3A4 (CYP3A4) modulation activity. Ternary and pseudo ternary diagrams were constructed to optimize the system. Peppermint oil and clove oil showed a high emulsification ability. The nature of obtained dispersions was identified to be nanoemulsions. Twenty-four formulations were evaluated for stability, robustness to dilution and self-emulsification efficiency. All formulations showed a very short emulsification time of <2min. The emulsification efficiency was significantly superior at pH6.8, at which the largest self-emulsifying region was also observed. Eight formulations were selected for further characterization according to cloud point measurement; mean droplet size, poly dispersity index (PDI) and zeta potential determination in addition to in vitro drug release study. All selected formulations showed very high cloud points (70–90°C), ultrafine mean droplet size (12±1.4 to 24.5±2.13nm), very low PDI values (0.015–0.1305) and almost a complete drug release after 12h. Formulation F15 (Peppermint oil 55% w/w: Cremophor RH40 25% w/w: Labrasol 20% w/w) was selected for further characterization. Its droplet size showed robustness to different dilution folds with different media and its TEM photograph showed spherical particles without any apparent aggregation even after 24h. Formulation F15 successfully controlled the systolic blood pressure of hypertensive rats for 24h with the maximum effect was observed after 2h. These results indicate that, SNEDDS could be promising delivery systems with a rapid onset of action and prolonged therapeutic effect of candesartan cilexetil.

Amiad UK moves to new facility

Amiad UK moves to new facility

Abstract 016: Combined AT 2 Receptor Stimulation/ AT 1 Receptor Blockade Does Not Cause Renal Dysfunction

Combined ACE inhibition and angiotensin type 1 receptor (AT 1 R) blockade (dual RAS) blockade) causes renal failure which limits their combined use. Angiotensin type 2 receptor (AT 2 R) stimulation evokes renoprotective effects but potential adverse renal effects in drug combination are not known. We examined the effects of the AT 2 R agonist compound 21 (C21) combined with either candesartan cilexetil or perindopril on renal function in a preclinical model that is predictive of clinical outcome. Adult (~25 week-old) male SHR were placed on a normal salt (0.35%, n=8) or a low salt (LS; 0.05%) diet for 17 days with rats on a LS diet randomised to receive one of the following treatments for the final 10 days: untreated (n=8); C21 (0.3mg/kg/d s.c., n=5); candesartan (2 mg/kg/d, n=6); perindopril (0.5mg/kg/d, n=5); C21+candesartan (n=8); C21+perindopril (n=5); or candesartan+perindopril (dual RAS blockade, n=7). Systolic arterial pressure (SBP) was measured via tail cuff at days 0, 7 and 17. At the end of the treatment, renal function was assessed by measuring plasma creatinine, urea, K+ and glomerular filtration rate (GFR) in conscious rats via transdermal assessment of elimination half-life kinetics of FITC-sinistrin (3-5mg/100g i.v.). Candesartan (-43±10 mmHg) or perindopril (-49±12 mmHg) reduced SBP to a similar extent alone or combined with C21, whereas dual RAS blockade markedly reduced SBP (-115±14 mmHg; P&lt;0.01 versus all groups). Plasma creatinine (424 ±65 μmol/L), urea (&gt;50 mmol/L cut-off) and K+ (5.94 ±0.82 mmol/L) levels were all significantly elevated by dual RAS blockade compared with untreated SHR on normal diet (creatinine 39 ±2 μmol/L; urea 7.08±0.22 mmol/L; K+ 4.23±0.13 mmol/L; all P&lt;0.01) or LS diet (creatinine 29 ±2 μmol/L; urea 5.2±0.57 mmol/L; K+ 4.29±0.17 mmol/L; all P&lt;0.01), whereas plasma measurements for C21+candesartan and C21+perindopril were similar to control groups. Estimated GFR in LS group (1.18±0.06 ml/min/100g BW) was similar to other groups except during dual RAS blockade where GFR was markedly impaired (0.32±0.10 ml/min/100g BW; P&lt;0.01 versus LS). Collectively, these data suggest that, unlike dual RAS blockade, an AT 2 R agonist combined with either ACE inhibition or AT 1 R blockade is not likely to cause renal dysfunction.

Forced Degradation Studies of Candesartan Cilexetil and Hydrochlorothiazide Using a Validated Stability-Indicating HPLC-UV Method

Forced degradation studies of candesartan cilexetil (CCX) and hydrochlorothiazide (HCTZ) were performed by using stressed drugs under acid, alkaline, and neutral hydrolysis; oxidation; photolysis; and thermal degradation conditions. A simple and specific method of high-performance liquid chromatography with UV detection was developed for simultaneous determination of CCX, HCTZ, and their degradation products. Optimum conditions were achieved with a running buffer mixture of acetonitrile and 10 mM phosphate buffer (pH 7.0; 32 : 68, v/v) at a flow rate of 1.0 mL/min using a Zorbax stable-bond cyano (SB CN) column (4.6 × 150 mm, 5 μm), 25°C column temperature, and 254 nm UV detection wavelength. This method was validated for linearity, range, accuracy, precision, and specificity according to International Conference on Harmonization (ICH) guidelines. All figures of merit for method validation are acceptable. The method proved to be stability-indicating because it also analyzed drugs in the presence of their degradation products with a resolution of the critical peak pair at least 1.5 and peak purity values greater than 990. CCX was stable under neutral hydrolysis, photolysis, and thermal degradation conditions but degraded under acid and alkaline hydrolysis and oxidation conditions. HCTZ was stable under oxidation, photolysis, and thermal degradation conditions but degraded under neutral, acid, and alkaline hydrolysis conditions.

Classification and Visualization of Physical and Chemical Properties of Falsified Medicines with Handheld Raman Spectroscopy and X-Ray Computed Tomography.

Analytical methods for the detection of substandard and falsified medical products (SFs) are important for public health and patient safety. Research to understand how the physical and chemical properties of SFs can be most effectively applied to distinguish the SFs from authentic products has not yet been investigated enough. Here, we investigated the usefulness of two analytical methods, handheld Raman spectroscopy (handheld Raman) and X-ray computed tomography (X-ray CT), for detecting SFs among oral solid antihypertensive pharmaceutical products containing candesartan cilexetil as an active pharmaceutical ingredient (API). X-ray CT visualized at least two different types of falsified tablets, one containing many cracks and voids and the other containing aggregates with high electron density, such as from the presence of the heavy elements. Generic products that purported to contain equivalent amounts of API to the authentic products were discriminated from the authentic products by the handheld Raman and the different physical structure on X-ray CT. Approach to investigate both the chemical and physical properties with handheld Raman and X-ray CT, respectively, promise the accurate discrimination of the SFs, even if their visual appearance is similar with authentic products. We present a decision tree for investigating the authenticity of samples purporting to be authentic commercial tablets. Our results indicate that the combination approach of visual observation, handheld Raman and X-ray CT is a powerful strategy for nondestructive discrimination of suspect samples.

Efficacy and Tolerability of Combination Therapy Versus Monotherapy with Candesartan and/or Amlodipine for Dose Finding in Essential Hypertension: A Phase II Multicenter, Randomized, Double-blind Clinical Trial

PurposeIntensive blood pressure (BP) lowering is important for the treatment of hypertension; however, it has been a challenge to achieve target BP in many patients. The purpose of this study was to explore the optimal dosage of a fixed-dose combination of candesartan cilexetil (CAN) and amlodipine besylate (AML), by examining the tolerability and efficacy of CAN/AML combination therapy compared with those of monotherapy with either drug in patients with essential hypertension. MethodsThis Phase II multicenter, randomized, double-blind clinical trial enrolled patients aged 19 years or older with essential hypertension, defined as a mean sitting diastolic BP (msDBP) between 95 and 115 mm Hg, and a mean sitting systolic BP (msSBP) of <200 mm Hg after a 2-week placebo run-in period. A total of 635 patients were screened, of whom 439 were randomized to receive treatment; 425 patients were included in the full analysis set (combination therapy, 212; monotherapy, 213). Participants were randomly assigned to receive 1 of 8 treatments: CAN (8 or 16 mg), AML (5 or 10 mg), CAN/AML (8 mg/5 mg, 8 mg/10 mg, 16 mg/5 mg, or 16 mg/10 mg), once daily for 8 weeks. FindingsAfter 8 weeks of treatment, changes in msDBP were significantly greater in the groups receiving CAN/AML combination therapies compared with monotherapies at matched doses, with the exception of CAN 8 mg/AML 10 mg versus AML 10 mg. The response to treatment and the achievement of target BP (both msSBP and msDBP) at week 8 were significantly greater overall in the groups that received combination therapy versus monotherapy. All medications were relatively well tolerated in each group. ImplicationsEight-week administration of CAN/AML (8 mg/5 mg, 16 mg/5 mg, and 16 mg/10 mg) resulted in a significantly greater BP reduction than that with CAN or AML monotherapy, and was determined to be well tolerated. ClinicalTrials.gov identifier: NCT02944734.

Tumor-targeting templated silica nanoparticles as a dual-drug delivery system for anti-angiogenic ovarian cancer therapy.

The present study indicated the successful construction of a silica nanoparticle (SLN)-based drug delivery system (DDS) for the tumor-targeted co-delivery of two anti-angiogenic drugs, candesartan (CD) and trastuzumab (Tra), for ovarian cancer therapy via different anti-angiogenic mechanisms using hyaluronic acid (HA)/Tra/CD/SLNs. In vitro and in vivo anti-angiogenic assays indicated that CD and Tra exert beneficial functions on suppressing cancer angiogenesis, and exhibited significantly enhanced effects compared with the angiotensin stimulated group (P<0.01). CD and Tra co-delivery also significantly increased the anti-angiogenic effect compared with applying either drug alone (P<0.01). Furthermore, HA on the surface of the DDS was demonstrated to reduce the cytotoxicity of the DDS and also endowed the particles with an advanced tumor-homing property in vitro and in vivo. The present results revealed that HA/Tra/CD/SLNs may be a preferable formulation for anti-angiogenic ovarian cancer therapy.

Synergistic Suppression of Tumor Angiogenesis by the Co-delivering of Vascular Endothelial Growth Factor Targeted siRNA and Candesartan Mediated by Functionalized Carbon Nanovectors.

Single-walled carbon nanotubes (SWNTs) with unique physicochemical properties have exhibited promising biomedical applications as drug and gene carriers. In this study, polyethylenimine (PEI)-modified SWNT conjugates linked with candesartan (CD) were developed to deliver vascular endothelial growth factor (VEGF)-targeted siRNA (siVEGF) for the synergistic and targeted treatment of tumor angiogenesis. The characterization results revealed that SWNT-PEI-CD conjugates were successfully synthesized and exhibited desirable dispersibility and superior stability. Confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) results showed that SWNT-PEI-CD/siVEGF complexes could achieve high cellular uptake and specific intracellular distribution of siRNA in AT1R overexpressed PANC-1 cells. Strong down-regulation of VEGF was also verified by qualitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot in complex-treated PANC-1 cells. The in vitro angiogenesis assay showed that SWNT-PEI-CD/siVEGF complexes highly inhibited tube formation of human umbilical vein endothelial cells. Furthermore, in vivo observation in PANC-1 xenografted nude mice demonstrated that SWNT-PEI-CD/siVEGF complexes exhibited significant distribution at tumor sites and caused obvious inhibition of tumor growth and tumor-associated angiogenesis repression induced by the drug combination of CD and siVEGF. Finally, a WST-1 assay indicated that SWNT-PEI-CD possessed low cytotoxicity, and a hemolysis test showed good biocompatibility of SWNT-PEI-CD. Hematological and histological analyses confirmed that SWNT-PEI-CD/siVEGF complexes did not cause any obvious toxic effects to blood and major organs. These findings suggested that the SWNT-PEI-CD/siVEGF co-delivery system with tumor-targeting specificity, improved endosomal escaping properties, and collaboration of angiogenesis inhibition could be a prospective method for efficient tumor antiangiogenic therapy.

The ameliorative effects of &lt;i&gt;Moringa oleifera&lt;/i&gt; leaf extract on cardiovascular functions and osmotic fragility of wistar rats exposed to petrol vapour

The present study was aimed at evaluating the ameliorating effects of Moringa oleifera extract compared to captopril and candesartan cilexetil on cardiovascular functions and osmotic fragility of rats exposed to petrol vapour. Twenty five adult male Wistar rats (130g-200g) were randomly grouped to five with five rats in a group. Group 1 (control) was not exposed to petrol fume. Groups 2 (petrol only), was exposed to petrol fume only. Groups 3, 4 and 5 were pretreated with Moringa oleifera extract (40mg/kg), captopril (25 mg/kg) and candesartan (16mg/kg), respectively before exposure to petrol vapour, 10 minutes every day for eight weeks. All groups were given feed and water ad-libitum. Petrol vapour was generated by using human compressor nebulizer adopted for rats and connected to fume chamber where the rats were kept. The pretreatment were administered by oral cannula. At the end of the exposure, 0.2ml of blood samples obtained from individual rat in each group were suspended in separate sets of Phosphate buffer saline (PBS) solution of decreasing concentrations. Erythrocyte osmotic fragility (EOF) was determined by spectrophotometer. Electrocardiography was done using EDAN 10. There was significant increase (p&lt;0.05) in EOF of the rats exposed to petrol vapour only. However, Moringa oleifera, captopril and candesartan cilexetil significantly ameliorated this effect. There was no significant difference in the amelioration of Moringa oleifera and candesartan cilexetil. There was absence of p-wave and significant increase in heart rate observed in the electrocardiogram of petrol only group, this was significantly restored in the Moringa oleifera, captopril and the candesartan cilexetil group. The results showed that exposure to petrol vapour elevated EOF, resulted in atria arrhythmia and increased heart rate. These effects were ameliorated by pretreatment with Moringa oleifera, captopril and candesartan cilexetil. The amelioration in Moringa oleifera was comparable with that of candesartan cilexetil suggesting that Moringa oleifera may be an Angiotensin II receptor blocker.Keywords: Candesartan cilexetil, Captopril, Moringa oleifera, Osmotic fragility, Petrol vapour