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The Arecaceae family contains wide classes of phytoconstituents and possesses wide range of pharmacological Activities members of this family are used in folk medicine for treatment of several diseases. Dypsis pembana (H.E.Moore) Beentje& J. Dransf. is a palm tree growing in Tanzania belongs to family Arecaceae. In this study, a detailed macromorphological characters of stem, leaf, inflorescence, flower, fruit in addition to micromorphological characters of the leaves of Dypsis pembana Family Arecaceae cultivated in Egypt were studied for the identification of the plant in both entire and powdered form, in addition to characterization of fatty acids of the leaves by GC-MS analysis. Thorough analysis of the chromatogram of the n-hexane fraction and careful matching examination of the acquired spectra resulted in identification of 12 phytochemicals and revealed the presence of saturated fatty acids mainly as Palmitic acid methyl ester, Lauric acid methyl ester, Methyl tetradecanoate, Methyl stearate , Margaric acid methyl ester, Eicosanoic acid methyl ester and Capric acid methyl ester and polyunsaturated fatty acids mainly as Linolenic acid methyl ester and Linoleic acid methyl ester in addition to other phytochemicals as 2,2-Dimethylocta-3,4-dienal , 3,7,11-Trimethyl-2,4-dodecadiene and 3,7,11,15-Tetramethyl-2-hexadecen-1-ol.
Carfilzomib (CFZ) is a second-generation proteasome inhibitor effective in blood cancer therapy. However, CFZ has shown limited efficacy in solid tumor therapy due to the short half-life and poor tumor distribution. Albumincoated nanocrystal (NC) formulation was shown to improve the circulation stability of CFZ, but its antitumor efficacy remained suboptimal. We hypothesize that NC size reduction is critical to the formulation safety and efficacy as the small size would decrease the distribution in the reticuloendothelial system (RES) and selectively increase the uptake by tumor cells. We controlled the size of CFZ-NCs by varying the production parameters in the crystallization-in-medium method and compared the size-reduced CFZ-NCs (z-average of 168 nm, NC168) with a larger counterpart (z-average of 325 nm, NC325) as well as the commercial CFZ formulation (CFZ-CD). Both CFZ-NCs showed similar or higher cytotoxicity than CFZ-CD against breast cancer cells. NC168 showed greater uptake by cancer cells, less uptake by macrophages and lower immune cell toxicity than NC325 or CFZCD. NC168, but not NC325, showed a similar safety profile to CFZ-CD in vivo. The biodistribution and antitumor efficacy of CFZ-NCs in mice were also size-dependent. NC168 showed greater antitumor efficacy and tumor accumulation but lower RES accumulation than NC325 in 4T1 breast cancer model. These results support that NC formulation with an optimal particle size can improve the therapeutic efficacy of CFZ in solid tumors.
Diabetes is a known risk factor for sexual dysfunction in men; diabetic men have an increased risk of erectile dysfunction compared to non-diabetic men. Canagliflozin is one of the common antidiabetic drugs that is readily used in the treatment of type-2 diabetes. Concomitantly phosphodiesterase 5 inhibitors, such as tadalafil, can be given to the patient to alleviate erectile dysfunction. Canagliflozin is reported to be one of the cytochrome P450 3A4 enzyme inhibitors, that might seriously influence blood concentration levels of tadalafil but there is no study till now, discussing this interaction. Therefore, a fast, simple, and sensitive high-performance thin-layer chromatographic method was developed, validated, and applied for the simultaneous determination of tadalafil and canagliflozin in spiked and real human plasma. The limit of detection for tadalafil was 0.14 ng/band and for canagliflozin was 0.16 ng/band. The limit of quantitation value for tadalafil was 0.43 ng/band and for canagliflozin was 0.47 ng/band. Tadalafil and canagliflozin were determined simultaneously in real human plasma using the described procedure and the method was applied for in vivo pharmacokinetic drug interaction study between the studied drugs, which proved significant interaction between them when administered simultaneously.
Erectile dysfunction (ED) is one of the most common chronic diseases affecting men and its incidence increases with aging. Due to its substantial influence on the quality of life, phosphodiesterase type-5 (PDE5) inhibitors have been implemented to treat ED by increasing the penile blood flow that results in improving erection. PDE5 inhibitors is a class of drugs that affects many pharmacological sectors, and it is essential to review the different analytical methods described for their determination. Few reviews were published concerning this group of drugs. For this reason, this review article gathers the different analytical methods used to determine PDE5 inhibitors in pharmaceutical and biological samples over the past 20 years. Different analytical techniques were used to analyze these compounds in different matrices such as separation methods (capillary electrophoresis, LC-MS, UPLC-MS/MS, and GC-MS), spectroscopic methods (UV-visible methods, FT-IR spectroscopy and spectrofluorometry) and electrochemical methods (polarography, voltammetry and potentiometry). This review focuses on the different electrochemical methods and their use in analytical determination of PDE5 inhibitors in pharmaceutical dosage forms and biological samples. Moreover, it discusses the different modified electrodes used for their electroanalytical determination and the behavior of the studied drugs at different modified electrodes. Additionally, this review discusses the pharmacokinetics of the studied compounds and their interactions with other co-administered drugs especially the metabolic interactions between the studied compounds and other co-administered drugs in different matrices. This literature survey would provide a beneficial guide for future analytical investigation of PDE5 inhibitors.