Trends in Pharmaceutical Sciences
Volume:6 Issue: 3, Sep 2020

Despite the extensive application of methotrexate (MTX) as a chemotherapeutic agent and an immune system suppressor, its therapeutic implementation has been limited due to its poor pharmacokinetics, saturable cellular transport, and insufficient response in some conditions. These limitations have resulted in the development of novel formulations. A pH-dependent MTX release was indicated in our previous study on polyethyleneimine nano-hydrogels; however, it exhibited a fast drug release in phosphate-buffered saline simulating physiologic pH and tonicity conditions. Thus, the current study was aimed at the synthesis of Zn(MTX)2Cl2 complex (MTX-Zn) to modulate drug loading and release under physiologic condition (pH=7.4). MTX-Zn was synthesized by the hydrothermal method and characterized by TLC, FT-IR spectroscopy, and Eriochrome Black T complexometric titration. MTX-Zn was then loaded into the nano-hydrogels and purified through ultrafiltration. The final product was evaluated by DLS, Zeta-potential, and TEM. The variations in the drug loading and release in acidic (tumor) and physiologic media were assessed through UV-Vis spectrophotometry and dialysis methods, respectively. A 5-fold enhancement was observed in the MTX solubility in the acetate buffer; while the Log D value increased from -0.66 to 0.1 upon Zn2+ complexation, reflecting an augmentation in the drug lipophilicity. The MTX-Zn loaded nano-hydrogels exhibited desirable physicochemical features like a small hydrodynamic diameter of 125.7 nm and low polydispersity (PDI = 0.14). The results indicated that, the release tests indicated that the release of MTX-Zn involves a combination of diffusion and swelling mechanisms. MTX-Zn complexation can be applied in the sustained drug release from the nano-hydrogel formulations.

Solenanthus circinatus root, commonly called “Azaar Choob” in Persian medicine, has a very long history of use in relieving pain and inflammation in muscle contusion and bone bruises and fractures. In this study, the analgesic effect of root extract and various fractions of S. circinatus were assessed in male rats using tail flick and formalin tests. Powdered roots of the plant was extracted with ethanol in a soxhlet apparatus and then fractionated with solvents of increasing polarity including petroleum ether, chloroform, ethyl acetate and n-butanol in a liquid-liquid extractor. Ethanolic extract and fractions were then chromatographed on silica gel TLC plates using various solvent systems. The spots on the chromatograms visualized using colour reagents which showed the presence of various compounds. In order to evaluate analgesic effect, rats were treated with 200 mg/kg of extract and fractions intraperitoneally and verified by tail-flick and formalin tests and compared with diclofenac group (25 mg/kg) as a standard drug. Extract and almost all fractions revealed significant analgesic effects compared to the control group. Based on the results, analgesic activity of root extract and fractions of S. circinatus were comparable with that of diclofenac. Petroleum ether fraction displayed higher pain relieving activity than diclofenac at 25 mg/kg in tail-flick test. Interestingly the analgesic efficacy of petroleum ether fraction surpassed other fractions at 60 min interval after injection. Ethyl acetate and petroleum ether were found to be superior to other fractions in manifestation of analgesic activity. The root extract is currently under further detailed investigation.

methotrexate (MTX) is a routinely used antifolate for the treatment of solid tumors and hematologic malignancies. However, high-dose MTX can lead to severe side effects and the patients are required to receive leucovorin rescue. Hence, we aimed to develop a fast and specific HPLC method for monitoring MTX level in sera of cancer patients. HPLC analysis was carried out on a Chromolith RP-18 monolithic column. The assay method was validated in terms of specificity, linearity, accuracy, precision, and limit of quantification. Using pharmacokinetic equations and limited blood sampling from each patient at 24 and 48 h after initiation of MTX therapy, it was attempted to predict the serum MTX level for discontinuation of leucovorin. the HPLC assay method was successfully validated for determination of the MTX level in combination with other concomitantly used drugs in the sera of cancer patients with a considerable decline in the analysis time (a total run time of less than 4 min). In addition, the HPLC assay method was favorably applied to the determination of MTX pharmacokinetic parameters using two-compartmental model approach. It was revealed that the MTX levels were in toxic range in some patients and the MTX pharmacokinetic parameters varied in range of 17-97% among the patients. monitoring the MTX level in patient serum, especially when prescribed in high doses, is highly demanded.

In the present study, the mixing behavior of different groups of surfactants and fatty acid bioconjugated L-asparaginase investigated. The amphiphilic macromolecules were achieved by covalent linkage of fatty acids with different chain lengths (C12, C16, and C22) to the native enzyme, L-asparaginase. The amino group of L-asparaginase lysine residue was conjugated to the carboxylic group of fatty acids, using a carbodiimide activator. The effect of different kinds of surfactants on particle size and enzyme activity of fatty acid bioconjugated L-ASNase was evaluated. The particle sizes of resulted micellar nanocarrier before and after lyophilization and enzyme activity investigated. Among all surfactants, pluronic F-127 with fatty acid bioconjugated L-asparaginase presented more plasma and PBS half-life. Higher activity value after lyophilization for bioconjugate with pluronic F-127 also achieved. These findings from L-asparaginase modification by fatty acid and surfactants indicate a promising stabilized product that may serve as a new candidate for medical purposes.

Cirrhosis-associated muscle mass loss or sarcopenia is a common complication (17-30% prevalence) in cirrhotic patients. However, the pathogenesis of this complication is poorly understood. Therefore, finding the mechanisms of sarcopenia could lead to the development of therapeutic strategies against this complication. In the current study, rats underwent bile duct ligation (BDL) surgery, and their skeletal muscle (gastrocnemius; GS) was isolated and assessed 28 and 56 days after BDL operation. Significant increase in biomarkers of oxidative stress, including reactive oxygen species (ROS) formation, lipid peroxidation, and increased oxidized glutathione (GSSG) levels were detected in the muscle of cirrhotic animals. Skeletal muscle tissue antioxidant capacity and reduced glutathione (GSH) were also significantly decreased in BDL rats. Moreover, deterioration of several mitochondrial indices, including mitochondrial depolarization, increased mitochondrial permeabilization, depleted ATP reservoirs, and decreased mitochondrial dehydrogenases activity, were evident in the GS isolated from cirrhotic rats. Based on these data, oxidative stress and mitochondrial impairment seem to play as primary mechanisms of cirrhosis-induced sarcopenia.

The plants with high amounts of polyphenolic constituents may act as antioxidants or as producer of other mechanisms causing to anticarcinogenic or cardioprotective actions. So, the objective of the present survey is quantitation of rosmarinic acid and caffeic acid as polyphenol compounds by means of high performance thin layer chromatography (HPTLC) in different Salvia genera such as Salvia santolinfolia, Salvia macilenta, Salvia comperesa, Salvia mirzayanii, and Salvia sharifii. The plant materials were collected from Hormozgan Province and methanolic extracts of them were studied by HPTLC. An HPTLC plate silica gel 60 F254 as stationary phase, toluene-ethyl acetate-formic acid with ratio of 67.72-22.90 and 9.38 %, repectively as mobile phase were selected and quantitation of rosmarinic acid and caffeic acid were done at 366 nm. It was found that S. comperesa (45.72±1.6 mg/g) and S. mirzayanii (464.64±0.028 mg/g) have higher amounts of rosmarinic acid and caffeic acid, respectively. Values of rosmarinic acid for other Salvia genera were obtained as; S. mirzayanii 8.50±0.46, S. santolinfolia 7.34±0.15, S. macilenta 5.64±0.18, and S. sharifii 4.52±0.11 mg/g for each of dried plants. Similar analysis for caffeic acid was achieved as 11.32±2.16 for S. santolinfolia, 5.22±1.13 for S. macilenta, 1.93±1.19 for S. comperesa, and for S. sharifii 4.63±3.26 mg/g for each of dried plants. In the developed method, Salvia officinalis was used as a standard module with amounts of 195.58 and 75.5 mg/g for rosmarinic acid and caffeic acid, respectively.

Management of ocular disease can be improved by prolonging the contact time of ophthalmic antibiotics with the ocular surface using bioadhesive polymers such as chitosan. Additionally, this polymer with antifungal and antibacterial activities could increase the antimicrobial effects of the antibiotics. In the present study, chitosan (CS) nanoparticles were investigated as a vehicle for ophthalmic delivery of sulfacetamide sodium. The ionotropic gelation method was used to fabricate chitosan -sulfacetamide sodium nanoparticles.  The effects of various factors including the concentration of CS, concentration of tripolyphosphate (TPP), and stirrer rate on the size of nanoparticles were studied. Different weight ratio of CS to sulfacetamide sodium on the encapsulation efficiencies of nanoparticles was assessed. The particles were prepared under the optimal condition of 0.45% CS concentration, 0.45% TPP concentration, stirrer rate at 6000 rpm. Their particle size was 72nm. In these particles with a 1:2 weight ratio of CS to sulfacetamide sodium, the encapsulation efficiency was 42%. In vitro release profile showed that sulfacetamide sodium could not be released sufficiently for 24 h. Future studies should focus on in vitro and in vivo antibacterial properties to evaluate their potential as an ocular delivery system.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide and are usually multifactorial medical conditions. Usually cardiovascular patients must follow a complicated treatment scheme, containing several drugs. Fixed dose combinations (FDCs) are pharmaceutical formulations containing two or more active ingredients in a one pill. FDCs can add multiple benefits to the treatment of CVDs including increased patient compliance, elimination of some side effects and the simultaneous blockage of multiple pathogenic links. The great prevelance of FDCs in modern therapy brings the necessity of developing new analytical methods for the simultaneous analysis of their components. Capillary electrophoresis (CE) was shown to be as a complementary and attractive alternative to the more frequently used chromatographic methods. CE advantages relate to the high efficiency of separation, rapid method developement, short analysis time and relatively low operational costs. The most frequently used CE techniques in the analysis of FDCs are capilllary zone electrophoresis (CZE) for ionized analytes and micellar electrokinetic chromatography (MEKC) for neutral ones. The current article reviews application of CE in the analysis of FDCs used in the treatment of CVDs.