Phytochemicals and bioactive compounds effective against acute myeloid leukemia: A systematic review.

This systematic review identified various bioactive compounds which have the potential to serve as novel drugs or leads against acute myeloid leukemia. Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy that arises from the dysregulation of cell differentiation, proliferation, and cell death. The risk factors associated with the onset of AML include long-term exposure to radiation and chemicals such as benzene, smoking, genetic disorders, blood disorders, advancement in age, and others. Although novel strategies to manage AML, including a refinement of the conventional chemotherapy regimens, hypomethylating agents, and molecular targeted drugs, have been developed in recent years, resistance and relapse remain the main clinical problems. In this study, three databases, PubMed/MEDLINE, ScienceDirect, and Google Scholar, were systematically searched to identify various bioactive compounds with antileukemic properties. A total of 518 articles were identified, out of which 59 were viewed as eligible for the current report. From the data extracted, over 60 bioactive compounds were identified and divided into five major groups: flavonoids, alkaloids, organosulfur compounds, terpenes, and terpenoids, and other known and emerging bioactive compounds. The mechanism of actions of the analyzed individual bioactive molecules differs remarkably and includes disrupting chromatin structure, upregulating the synthesis of certain DNA repair proteins, inducing cell cycle arrest and apoptosis, and inhibiting/regulating Hsp90 activities, DNA methyltransferase 1, and histone deacetylase 1.

Toxicity of Nanoparticles in Biomedical Application: Nanotoxicology.

Nanoparticles are of great importance in development and research because of their application in industries and biomedicine. The development of nanoparticles requires proper knowledge of their fabrication, interaction, release, distribution, target, compatibility, and functions. This review presents a comprehensive update on nanoparticles' toxic effects, the factors underlying their toxicity, and the mechanisms by which toxicity is induced. Recent studies have found that nanoparticles may cause serious health effects when exposed to the body through ingestion, inhalation, and skin contact without caution. The extent to which toxicity is induced depends on some properties, including the nature and size of the nanoparticle, the surface area, shape, aspect ratio, surface coating, crystallinity, dissolution, and agglomeration. In all, the general mechanisms by which it causes toxicity lie on its capability to initiate the formation of reactive species, cytotoxicity, genotoxicity, and neurotoxicity, among others.

HPTLC Method for Estimation of Topiramate in Solubility Studies, Diffusion Studies, Plasma, Brain Homogenate and Pharmaceutical Formulation.

Topiramate, 2,3:4,5-bis-O-(1-methylethylidene)-ß-d-fructopyranose, is an anticonvulsant drug indicated in the treatment and control of partial seizures and severe tonic-clonic (grand mal) seizures in adults and children. An economic and rapid high-performance thin-layer chromatographic (HPTLC) method was developed and was validated for the quantitative determination of topiramate in plasma, brain homogenate and pharmaceutical formulation. The simple extraction method was used for the isolation of topiramate from formulation, plasma and brain homogenate samples. HPTLC separation was achieved on an aluminum-backed layer of silica gel 60F254 plates using toluene : acetone (5.0 : 2.0, v/v) as mobile phase. Spots of developed plates were visualized by spraying of reagent [3.0% phenol in the mixture of ethanol : sulfuric acid (95 : 5, v/v)]. Quantitation was achieved by densitometric analysis at 340 nm over the concentration range of 1,000-5,000 ng/spot. The method was found to give compact spot for the drug (Rf: 0.61 ± 0.018). The regression analysis data for the calibration plots showed good relationship with a correlation coefficient of 0.9983. The minimum detectable amount was found to be 165 ng/spot, whereas the limit of quantitation was found to be 500 ng/spot. Statistical analysis of the data showed that the method is precise, accurate, reproducible and selective for the analysis of topiramate. The developed method was successfully employed for the estimation of topiramate in samples of equilibrium solubility study, diffusion study, microemulsion formulation and suspension formulation (developed in-house), rat plasma and rat brain homogenate samples.

Sensitive and robust methods for simultaneous determination of beclomethasone dipropionate and formoterol fumarate dihydrate in rotacaps.

Fixed dose combination containing beclomethasone dipropionate (BDP) and formoterol fumarate dihydrate (FFD) is used in the treatment of asthma in form of dry powder inhaler. Two methods are described for the simultaneous determination of BDP and FFD in commercial rotacap formulation. The first method was based on HPTLC separation of the two drugs followed by densitometric measurements of their spots at 220 nm. The separation was carried out on Merck HPTLC aluminum sheets precoated with silica gel 60F254 using hexane:ethyl acetate:methanol:formic acid (2.0:2.5:2.0:0.2, v/v/v/v) as mobile phase. The linearity was found to be in the range of 2.4-8.4 µg/spot and 80-280 ng/spot for BDP and FFD, respectively. The second method was based on HPLC separation of the two drugs on the reversed phase Enable HPLC Analytical C18 G 120Å (250 × 4.6 mm, 5 µm) column at ambient temperature using a mobile phase consisting of methanol:acetonitrile:phosphate buffer adjusted to pH 3.6 using orthophosphoric acid (65:25:10, v/v/v). Quantitation was achieved with UV detection at 220 nm based on peak area with linear calibration curves at concentration ranges of 10-200 and 0.3-6.0 µg/mL for BDP and FFD, respectively. Both methods were validated in terms of precision, robustness, recovery and limits of detection and quantitation. The robustness of both methods was assessed using experimental design and results were analyzed by statistical and graphical approaches. Rotacaps formulation containing BDP (200/400 µg) and FFD (6 µg) were successfully quantified using the proposed methods. The proposed methods can be used as sensitive, precise, accurate and robust methods for quantification of BDP and FFD in Rotacaps.

Hydrochloride salt co-crystals: preparation, characterization and physicochemical studies.

Co-crystallization approach for modification of physicochemical properties of hydrochloride salt is presented. The objective of this investigation was to study the effect of co-crystallization with different co-crystal formers on physicochemical properties of fluoxetine hydrochloride (FH). FH was screened for co-crystallization with a series of carboxylic acid co-formers by slow evaporation method. Photomicrographs and melting points of crystalline phases were determined. The co-crystals were characterized by FTIR, DSC and PXRD methods. Solubility of co-crystals was determined in water and buffer solutions. Powder and intrinsic dissolution profiles were assessed for co-crystals. Physical mixtures of drug and co-formers were used for comparisons at characterizations and physicochemical properties evaluation stages. Four co-crystals of FH viz. Fluoxetine hydrochloride-maleic acid (FH-MA), Fluoxetine hydrochloride-glutaric acid (FH-GA), Fluoxetine hydrochloride-L-tartaric acid (FH-LTA) and Fluoxetine hydrochloride-DL-tartaric acid (FH-DLTA) were obtained from screening experiments. Physical characterization showed that they have unique crystal morphology, thermal, spectroscopic and X-ray diffraction properties. Solubility and dissolution studies showed that Fluoxetine hydrochloride-maleic acid co-crystal possess high aqueous solubility in distilled water, pH 4.6, 7.0 buffer solutions and dissolution rate in distilled water than that of pure drug. Co-crystal formation approach can be used for ionic API to tailor its physical properties.