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Inflammation is a nonspecific response of tissues to diverse stimuli and/or insults associated with the release of various mediators that induce pain, fever, and general sense of illness. Such responses can be reduced by the administration of non-steroidal or steroidal anti-inflammatory drugs. These anti-inflammatory drugs are associated with various side effect. However, the combination of non-steroidal anti-inflammatory drugs (NSAIDs) with glucocorticoids provides a synergistic anti-inflammatory and pain relief with less side effects. In this study, we aimed to synthesize a novel twin-drug of Dexamethasone-Diclofenac formulated into polylactide (PLA) nanoparticles to improve their solubility and provide a sustained release system. The twin-drug was synthesized through an esterification reaction which was then encapsulated into PLA nanoparticles. The hydrolysis of the synthesized twin-drug and drug release from PLA nanoparticles were studied in vitro with and without esterase enzyme. The anti-inflammatory activity was studied in BALB/c mice. After the successful synthesis of the twin-drug, its water solubility was improved by its encapsulation into PLA nanoparticles with a loading capacity of 66%. The in vitro release showed a sustained release profile of the twin-drug up to 52 h. The esterase hydrolysis showed a rapid release with a maximum hydrolysis after 1.5 h. Moreover, the anti-inflammatory activity exhibited a synergistic effect with a higher percentage of inhibition for the TNF-α level in comparison to the parent drugs after 6 h treatment. In conclusion, the prepared nano twin-drug is a novel therapy that showed a sustained release profile with an excellent anti-inflammatory activity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Single walled carbon nanotubes (SWCNT) are currently under intensive investigation by many labs all over the world for being promising candidates for cancer chemotherapy delivery. On the other hand, combretastatin A4 (CA4) is an anticancer drug that induces cell apoptosis by inhibiting tubulin polymerization. However, it has the disadvantage of low water solubility and the non-selective targeting. Therefore, we aim to create nano-drug from the functionalization of SWCNT covalently with CA4 through click reaction in the presence of tetraethylene glycol linker in order to improve its dispersibility. Scanning electron microscopy and transmission electron microscopy showed good dispersibility of the functionalized SWCNT with diameters of 5-15 nm. Moreover, thermogravometric analysis showed that the efficiency of SWCNT functionalization was around 45%. The in vitro release profile of CA4 at physiological conditions showed that approximately 90% of the loaded drug was released over 50 h. After that MTS test was used to determine the suitable concentration range for the in vitro investigation of the SWCNT-CA4. After that the cytotoxic activity of the SWCNT-CA4 was evaluated by flow cytometry using annexin V/propidium iodide (PI) test. In comparison with free CA4, SWCNT-CA4 treatment demonstrated a significant increase in necrotic cells (around 50%) at the expense of the proportion of the apoptotic cells. Moreover, cell cycle PI test demonstrated that free CA4 and SWCNT-CA4 caused G2/M arrest. However with CA4 treatment higher proportion of cells were in the S-phase while with SWCNT-CA4 treatment greater proportion of cells appeared to be in the G1-phase. Taken together, the provided data suggest that the novel SWCNT-CA4 has a significant anticancer activity that might be superior to that of free CA4.

Background: Nanomedicine is the medical application of nanomaterials that may have an infinite size with the range less than 100 nm. This science has provided solutions to many of the current limitations in the diagnosis and treatment of diseases. Therefore, the pharmacist's knowledge and awareness of nano-pharmaceutical drugs will increase their availability in the market, and will improve the patient's compliance to their drug therapy. This study aimed to determine the availability of nano-pharmaceutical drugs in Palestinian hospitals and evaluate the extent of pharmacist's knowledge about them., Methods: A cross-sectional study design questionnaire was used to determine the availability of nano-pharmaceutical drugs based on the database of the ministry of health in the Palestinian hospitals (governmental, private and non- governmental organizations). Moreover, the knowledge of these nano-pharmaceutical drugs among pharmacists working in Palestinian hospitals was assessed based on developed questionnaire from the literature of the pharmaceutical formulations and nano-formulations. The variables were analyzed using Statistical Package for Social Sciences (SPSS 22)., Result: Fifty six pharmacists from 27 hospitals in the West bank completed the survey. The results regarding the availability of nano-pharmaceutical drugs indicated only eight available in hospitals with a frequency range 0-39.3%. Moreover, pharmacist's knowledge in the pharmaceutical formulations was better than that in nano-formulations., Conclusions: The availability of nano-pharmaceutical drugs in Palestinian hospitals was not adequate due to the lack of various nano-pharmaceutical drugs. The knowledge among pharmacists regarding nano-pharmaceutical drugs should be improved by providing courses in nanomedicine during the undergraduate pharmacy programs.

Background: Statins are the first-line therapy for lowering high lipid levels. Atorvastatin calcium (AtC) is the most commonly prescribed statin. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which converts HMG-CoA into mevalonic acid, a cholesterol precursor., Objective: To compound and evaluate the stability of AtC suspension (0.4% w/v) using commercial tablets or pure AtC powder as the source of the active pharmaceutical ingredient., Method: Several AtC suspension formulations were produced using commercial AtC tablets or AtC pure powder as the source of the active ingredient. The most suitable one in terms of general organoleptic properties and dissolution was selected for stability studies. For this purpose, samples of final suspensions were stored at room temperature and in the refrigerator. Assay, pH, organoleptic properties and microbial contamination were evaluated according to the USP specifications. High performance liquid chromatography was used for the analysis and quantification of AtC in the studied samples., Results: The obtained suspension (S4) had good organoleptic properties. It showed complete dissolution of AtC within 30 min. However, the suspension prepared from crushed tablet (S t 4) showed a better dissolution profile than that prepared from pure powder (S p 4). The prepared formula had unchanged pH, which remained around 9.9. S t and S p formulas were both free from microbial contamination. Both products showed good stability within at least the period of use of the 100 mL AtC bottles., Conclusions: AtC extemporaneous suspension was successfully prepared using tablets as a source of AtC or pure AtC powder. However, S t 4 had a better dissolution profile than S p 4. This study provides a solution for patients with swallowing difficulties or feeding tubes who are unable to take medicines in solid oral dosage forms. Community pharmacists can prepare the suspension using AtC tablets as the source of the active ingredient., Competing Interests: Competing interests: None declared.

Introduction: Interest in essential oils was recently revived with their popularity increasing in medicine, pharmacy, and aromatherapy. This study was performed to identify the chemical compositions of the essential oil of Ruta chalepensis growing wildly in three regions in Palestine and to assess and compare their antimicrobial and antioxidant activities., Methods: Identification of the essential oil was performed by gas chromatography coupled with mass spectrometry (GC-MS). Antimicrobial activity was tested against Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , Methicillin-Resistant Staphylococcus aureus , and Candida albicans by using minimum inhibitory concentration (MIC) assay, while antioxidant activity was analyzed by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method., Results: The essential oils of R. chalepensis from Jerusalem and Hebron regions have almost identical components; the major compounds identified were linalyl acetate and β -linalool; these essential oils exerted potential antioxidant and antibacterial activities. On the other hand, the major components of the plant essential oil from Jenin region were 2-undecanone and 2-nonanone, which exhibited potential antifungal activity., Conclusions: The phytoconstituents and antioxidant and antimicrobial properties of the essential oil of R. chalepensis from different regions in Palestine were established in this study. The obtained results indicate possible applications for R. chalepensis in the treatment of various infectious and noninfectious diseases.

The aim of this study was to develop an extemporaneous valsartan suspension (80 mg valsartan/5 mL) starting from commercial tablets (80-mg/ tablet). A high-performance liquid chromatographic system was used for the analysis and quantification of valsartan in the samples studied. Samples of valsartan suspension for analysis were prepared as reported by the validated high-performance liquid chromatographic method and the dissolution tests were performed according to the U.S. Food and Drug Administration's method. The high-performance liquid chromatographic assay indicated that the 80-mg/5-mL valsartan suspension was stable for 30 days when stored at long-term and accelerated storage conditions. Valsartan release profile showed that approximately 85% of valsartan dissolved after 10 minutes and, accordingly, the calculation of similarity factor was not necessary. It is possible for the pharmacist to crush valsartan 80-mg tablets and prepare a suspension which has dosage flexibility that can be calculated according to body-surface area, kidney, and liver functions, without affecting the chemical stability of the active ingredient nor its dissolution profile and also have a cost-effective dosage form.

Herein, we describe the first report on a new class of disk-shaped and quite monodisperse water-soluble nanomaterials that we named glyconanosomes (GNS). GNSs were obtained by sliding out the cylindrical structures formed upon self-organization and photopolymerization of glycolipid 1 on single-walled carbon nanotube (SWCNT) sidewalls. GNSs present a sheltered hydrophobic inner cavity formed by the carbonated tails, surrounded by PEG and lactose moieties. The amphiphilic character of GNSs allows the water solubility of insoluble hydrophobic cargos such as a perylene-bisimide derivative, [60]fullerene, or the anti-carcinogenic drug camptothecin (CPT). GNS/C60 inclusion complexes are able to establish specific interactions between peanut agglutinin (PNA) lectin and the lactose moiety surrounding the complexes, while CPT solubilized by GNS shows higher cytotoxicity toward MCF7-type breast cancer cells than CPT alone. Thus, GNS represents an attractive extension of nanoparticle-based drug delivery systems.

We present a mild and practical carbon nanotubes rings (CNRs) synthesis from non-covalent functionalized and water-soluble linear single-wall carbon nanotubes. The hemi-micellar-supramolecular self-organization of lactose-based glycolipid 1 on the ring surface, followed by photo-polymerization of the diacetylenic function triggered by UV light afforded the first water-soluble and biocompatible CNRs. The obtained donut-like nanoconstructs expose a high density of lactose moieties on their surface, and are able to engage specific interactions with Arachis hypogea lectin similar to glycoconjugates on the cell membrane.

We have investigated the cardioprotective effects of exercise training and/or curcumin on lead acetate-induced myocardial damage. Forty rats were randomly divided into 5 groups: (1) lead acetate, (2) curcumin, (3) endurance training, (4) training + curcumin, (5) sham groups. The rats in groups 3 and 4 experienced the treadmill running of 15 to 22 m/min for 25 to 64 minutes, 5 times a week for 8 weeks. Groups 1 to 4 received lead acetate (20 mg/kg), the sham group received curcumin solvent (ethyl oleat), and the curcumin and training + curcumin groups received curcumin solution (30 mg/kg) intraperitoneally. Lead administration resulted in significant increases in high-sensitivity C-reactive protein (hs-CRP), creatine kinase-MB (CK-MB), malondialdehyde (MDA), and low-density lipoprotein (LDL), and significantly decreased glutathione peroxidase (GPx), Total Antioxidant Capacity (TAC), and high-density lipoprotein (HDL) levels. Treadmill running and\or curcumin supplementation resulted in a significant decrease in hs-CRP, CK-MB, MDA, and LDL levels and significantly increased GPx, TAC, and HDL levels. These results suggest a lifestyle-induced cardioprotective potential in ameliorating lead-induced cardiotoxicity.

Supramolecular self-assembly of conjugated diacetylenic amphiphile-tethered ligands photopolymerize to afford polydiacetylene (PDA) functional liposomes. Upon specific interaction with a variety of biological analytes in aqueous solution, PDA exhibits rapid colorimetric transitions. The PDA nanoassemblies, which are excellent membrane mimics, include an ene-yne polymeric reporter responsible for the chromatic transitions and the molecular recognition elements that are responsible for selective and specific binding to the biological target. A bottleneck in the fabrication of these colorimetric biosensors is the preparation of the diacetylenic monomer embedded with the recognition element of choice. In the present work, we make use of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as key step in the preparation of sugar-coated liposome biosensors. The regioselective click ligation of the triacetylenic N-(2-propynyl)pentacosa-10,12-diynamide (NPPCDAM) with a variety of mannose- and lactose-tethered azides afforded chemo- and regioselectively the corresponding 1,2,3-triazole. The obtained diacetylenic monomers were incorporated efficiently into vesicles to afford functional mannose- and lactose-coated glycoliposomes. The obtained PDA-based click glycoliposomes have been characterized by using transmission electronic microscopy (TEM), dynamic light scattering (DLS), and UV/Vis spectroscopy. The efficiency of the reported approach was demonstrated by the rapid optimization of the hydrophilic spacer between the lipidic matrix and the mannose head group for the colorimetric detection of Concavalin A., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: To present a technical modification of the classic dismembered pyeloplasty technique. We have implemented it in 112 pyeloplasties performed during the past 15 years., Technical Considerations: The technical modification is based on a renal pelvis flap kept undetached from the ureteropelvic junction, and consequently from the ureter, until near completion of the new ureteropelvic anastomosis. This flap is used for ureteral handling (a "no touch" technique) during pyeloplasty and also serves as a very reliable guide for lateral ureteral spatulation, preventing ureteral twisting and subsequent misalignment of the de novo ureteropelvic junction. We experienced early complications in 4 patients (3.6%). Two patients had excessive urinary leakage from the ureteropelvic anastomosis because of misplacement of a Nelaton retroperitoneal tube drain. We have used soft Penrose drains for retroperitoneal drainage since. Two other patients needed reoperation because of a redundant renal pelvis and ureter consequent to a remnant high anastomosis and insertion of the ureter to the renal pelvis with subsequent kinking and obstruction. No other early or late complications attributable to obstruction of the anastomosis resulting from devascularization or misalignment between the ureter and renal pelvis were encountered., Conclusions: Modification of the classic pyeloplasty technique has proved relatively easy and reliable in our experience. With the increasing popularity of the laparoscopic approach for pyeloplasty, the described technical modification may become useful for laparoscopic handling of the ureter.

Objectives: To determine the value of the combined use of non contrast computerized tomography (NCCT) and dynamic renal scintigraphy (DRS) in the evaluation of patients with renal colic., Methods: Forty-nine consecutive patients with renal colic were evaluated with abdominal plain films (KUB), NCCT and DRS with Tc-99m DTPA or MAG-3. NCCT results showed size and location of the urolithiasis, as well as secondary signs of obstruction. DRS was used to determine the degree of obstruction in the affected renal unit. Patients were submitted to urologic intervention or followed, decision made on the basis of clinical symptoms, degree of obstruction, size, and location of the stone., Results: Three patients had other etiologies than stone for their symptoms and were excluded from the study. Of the remaining 46 patients, KUB detected stones in 24 (52.2%), while NCCT in all. NCCT showed secondary signs of obstruction in 35 patients (76%). Seven patients in this group (15%) had severe hydronephrosis on NCCT and complete obstruction on DRS. Twenty-eight patients (61%) showed moderate hydronephrosis and/or peri-renal and peri-ureteral stranding on the NCCT. In this latter group, DRS diagnosed complete obstruction in 5 (18%) patients, partial obstruction in 16 (57%) and no signs of obstruction in 7 (25%) patients. Overall 34% (12/35) of the patients with secondary signs of obstruction on NCCT had complete obstruction on DRS. NCCT revealed no secondary signs of obstruction in 11 patients (24%) with partial obstruction diagnosed by DRS in one of them (9%). All 12 patients with complete obstruction on the DRS underwent early intervention. Of the 16 patients with partial obstruction of the DRS, two patients (12.5%) necessitated ureteric stent insertion. Three patients with no obstruction on the RNS underwent elective extracorporal shock wave lithotripsy (ESWL) while the rest of the patients were followed and passed their stones spontaneously., Conclusions: The combination of non-enhanced helical CT and DRS assesses both anatomy and function. When NCCT shows no secondary signs of obstruction, NCCT as the sole imaging study performed may be adequate. If there are secondary signs of obstruction on NCCT, DRS can distinguish patients with different degrees of obstruction and together with the clinical course, size, and location of the lithiasis may help in selecting patients who need earlier intervention from those who may be safely observed.

An automated system to perform titration and standard addition in monosegemented flow analysis by employing the simultaneous multiple injection is described. The system was controlled by aPC-AT-386 microcomputer through a home-made parallel interface, employing a diode array spectrophotometer as detector. Software was written in QuickBasic 4.5 to control the system and for data acquisition. A three-way solenoid valve was used in conjunction with a proportional injector to add the titrant solution or the standard solution to the sample, to carry out titration or standard addition, respectively. Only one standard solution was used in each procedure and different quantities of titrant or standard were added to the sample by controlling the time interval in which the solenoid valve was switched on. Titration and standard addition curves similar to those of the manual methods were obtained in both cases, since the sample dispersion was very low due to the air bubbles of the monosegment. The titration system was evaluated through the determination of Fe(II) with a KMnO4 standard solution in pharmaceutical preparations. The standard addition process was assessed by determining Cr(VI) in natural waters and domestic wastewater using the diphenylcarbazide method. The results obtained in both methodologies did not differ significantly from the reference methods at a 95% confidence level.