Indometacin loading and in vitro release properties from novel carbopol coated spherical mesoporous silica nanoparticles

Spherical MCM-41 silica nanosized particles were synthesized and post synthesis modified by 3-aminopropyltriethoxysilane (APTES) in order to prepare amino-functionalized carrier. Both types of silica particleswere loaded with indometacin and further coated with carbopol. The preservation of morphology and pore structure of the particles was observed by XRD, TEM and N2 physisorption. FT-IR spectroscopy revealed the interaction between carboxyl groups of indometacin and the amino groups of the functionalized MCM-41. Amino-functionalization of the carrier resulted in higher degree of indometacin loading in comparison to the parent MCM-41, 39% vs. 30%, respectively. The coating of drug loaded amino-MCM-41 silica particles with carbopol significantly reduced the initial burst release of indometacin. Both silica carriers demonstrated no cytotoxicity on HL-60 (acute myeloid leukemia) and K-562 (chronic myeloid leukemia) cell lines

Palladium Complexes with 3-Substituted Derivatives of 5-Methyl-5-(4-pyridyl)hydantoins. Synthesis, Study and in vitro Cytotoxicity

Six palladium(II) and palladium(IV) complexes with 3-ethyl-5-methyl-5-(4-pyridyl)hydantoin, 3-propyl-5-methyl-5-(4-pyridyl)hydantoin and 3-benzyl-5-methyl-5-(4-pyridyl)hydantoin were synthe-sized. The complexes were identified and characterized by elemental analysis, IR, 1H, 13C NMR spec-tra etc. On the data obtained the molecular formulae of the new palladium complexes were proposed. The cytotoxicity of the complexes was evaluated in vitro using a panel of human tumour cell lines. The re-sults demonstrate that the Pd(II) complex with 3-benzyl-5-methyl-5-(4-pyridyl)hydantoin exerts cyto-toxicity as compared to the other studied Pd(II) complexes in all tested cell lines

Synthesis, Characterization, and Cytotoxic Activity of New Lanthanum(III) Complexes of Bis-Coumarins

Complexes of lanthanum(III) with bis-coumarins: 3,3′-benzylidene-bis(4-hydroxy-2H-1-benzopyran-2-one) (H(2)L1) and bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-(1H-pyrazol-3-yl)-methane (H(2)L2) were synthesized by reaction of lanthanum(III) salt and the ligands, in amounts equal to metal : ligand molar ratio of 1 : 2. The complexes were prepared by adding an aqueous solution of lanthanum(III) salt to an aqueous solution of the ligand subsequently raising the pH of the mixture gradually to circa 5.0 by adding dilute solution of sodium hydroxide. The lanthanum(III) complexes with bis-coumarins were characterized by different physicochemical methods—elemental analysis, IR-, (1)H-, and (13)C-NMR-spectroscopies, and mass spectral data. The spectral data of lanthanum(III) complexes were interpreted on the basis of comparison with the spectra of the free ligands. This analysis showed that in the La(III) complexes, the ligands coordinated to the metal ion through both deprotonated hydroxyl groups. On the basis of the ν(C=O) red shift observed, participation of the carbonyl groups in the coordination with the metal ion was also suggested. In the present study, we performed a cytotoxic-effects screening of the lanthanum complexes with H(2)L1 and H(2)L2 in a panel of human tumor cell lines, using the standard MTT-dye reduction assay for cell viability. The panel consisted of the acute myeloid leukemia-derived HL-60 and the chronic myeloid leukemia-derived BV-173. Following a 24- hour treatment of BV-173 cells with lanthanum complex of H(2)L1 at 100 or 200 μM led to a DNA-laddering. The findings suggest that the observed cytotoxicity of the lanthanum complex of H(2)L1 on BV-173 is at least partly mediated through induction of programmed cell death

Curcumin‘s Therapeutic Potential

Куркумата (Curcuma longa L., сем. Zingiberaceae) е подправка, която е широко използвана в индийската медицина. В спектъра на заболяванията, при които намира приложение, влизат жлъчни и чернодробни заболявания, безапетитие, синузит, ревматизъм, навяхвания и рани. Основното биологично активно вещество в корена от куркума е куркуминът, съпътствано от други близкородствени съединения. За терапевтичния потенциал на куркумина има редица данни от експериментални изследвания, както и клинични данни. Многобройни проучвания показват, че той има значителна противотуморна и в частност противомиеломна активност и откриват перспектива за бъдещото му приложение като лекарствен продукт. Лабилността му при орално приложение, както и потенциалните лекарствени взаимодействия с различни медикаменти, ограничават неговото свободно приложение под формата на капсулни и таблетни форми, но приемът му като подправка е показал само и единствено ползи за употребяващите го.Turmeric (Curcuma longa L., Zingiberaceae) is a spice that is widely used in Indian medicine. The spectrum of diseases in which it is applied includes bile and liver diseases, dizziness, sinusitis, rheumatism, sprains and wounds. The main biologically active substance in the turmeric root is curcumin, accompanied by other closely related compounds. For the therapeutic value of curcumin, there are a number of data from experimental studies as well as clinical data. Numerous studies have shown that it has significant anti-tumor and, in particular, anti-myeloma activity, and have discovered prospects for its future use as a medicinal product. Its lability in oral administration as well as potential drug interactions with various drugs restrict its free use in the form of capsule and tablet formulations, but its administration as a spice has only shown benefits to the patients

New Samarium(III), Gadolinium(III), and Dysprosium(III) Complexes of Coumarin-3-Carboxylic Acid as Antiproliferative Agents

New complexes of samarium(III), gadolinium(III), and dysprosium(III) with coumarin-3-carboxylic acid (HCCA) were prepared by the reaction of the ligand with respective metal nitrates in ethanol. The structures of the final complexes were determined by means of physicochemical data, elemental analysis, IR and Raman spectra. The metal-ligand binding mode in the new Ln(III) complexes of coumarin-3-carboxylic acid was elucidated. The vibrational study gave evidence for bidentate coordination of CCA− to Ln(III) ions through the carbonylic oxygen and the carboxylic oxygen atoms. The complexes were tested for antiproliferative activitiy on the chronic myeloid leukemia-derived K-562, overexpressing the BCR-ABL fusion protein. Cytotoxicity towards tumor cells was determined for a broad concentration range. The samarium salt exerted a very weak antiproliferative effect on these cells. This is in contrast to the lanthanide complexes, especially samarium complex, which exhibited potent antiproliferative activity. The present study confirms our previous observations that the lanthanide complexes of coumarins exhibit antiproliferative activity towards K-562 cell line

Cannabinoids Usage In The Fight Against Oncological Diseases

През последното десетилетие класическата химиотерапия отстъпва място на нови фармакологични подходи, насочени към патологично изменените сигнално-трансдукционни пътища. Канабисът е една от множеството древни билки използвани от американските индианци от хилядолетия насам. В наши дни научните данни за ползотворните му ефекти при широк спектър от заболявания непрекъснато нарастват. Има много експериментални данни, както и експериментални модели и при хора изследващи, повлияваните от биологично активните вещества в него, сигнални каскади.В този обзор са описани редица изследвания и клинични проучвания, които показват значителния напредък постигнат последните години при изпозлването на канабиноидите за борба с онкологичните заболявания. Няколко проучвания in vivo и in vitro доказват добрата поносимост и безопасност на канабидиола при хора и животни. Положителния ефект на субстанцията при различни състояния, възпалителни и онкологични трябва да бъде отчетен, но за да навлезе по-пълно в медицинската практика са необходими още много задълбочени проучвания.Over the last decade, classical chemotherapy has given way to new pharmacological approaches aimed at pathologically altered signal transduction pathways. Cannabis is one of the many ancient herbs used by American Indians for millennia. Nowadays, scientific data on its beneficial effects over a wide range of diseases are constantly increasing. There are many experimental data, as well as experimental models, and in humans studying the signal cascades influenced by the biologically active substances in it.This review describes a number of studies and clinical trials that show the significant advances made in recent years in the use of cannabinoids to combat oncological diseases. In vivo and in vitro studies demonstrate the good tolerability and safety of cannabidiol in humans and animals. The positive effect of the substance in various conditions, inflammatory and oncological, should be taken into account, but more extensive research is needed to gain access to medical practice

Prognostic value of plasmablastic morphology and p21, p53 and Cyclin D1 expression in myeloma cells: retrospective study of 122 patients with first time diagnosed Multiple Myeloma

Print version of the article - 2021, published online - 2022.Multiple myeloma (MM) is the most common bone marrow malignancy which is defined with bone marrow infiltration of more than 10% of terminally differentiated plasma cells sive myeloma cells. The aim of this study was to find correlations between the expression of some immunohistochemical markers (Cyclin D1, p53, p21), plasmablastic differentiation and prognosis of MM. Immunohistochemistry was used to detect expression of cell cycle proteins. Bone marrow trephine biopsies of 122 MM patients were analysed to determine the plasmablastic morphology of myeloma cells and myeloma cells expression of immunohistochemical markers (p21, p53, Cyclin D1). The following clinical data of MM patients were obtained: ß2-microglobulin, albumin, haemoglobin, platelet count, glomerular filtration rate (GFR), creatinine, calcium level, M-gradient and presence of osteolytic lesions. These data were compared with the bone marrow histological findings. Plasmablastic differentiation correlated with decreased level of haemoglobin, albumin and GFR. Cyclin D1 expression correlated with significantly higher serum calcium level, more common osteolytic lesions in bones. Patients with p21 expression in myeloma cells had lower albumin levels, higher M-gradient levels and more advanced stage by Salmon – Durie. These results suggest that there are correlations between plasmablastic differentiation, expression of p53, CyclinD1 and p21 and poor prognosis in cases of MM.publishersversionPeer reviewe

Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems

Curcumin is a perspective drug candidate with pleiotropic antineoplastic activity, whose exceptionally low aqueous solubility and poor pharmacokinetic properties have hampered its development beyond the preclinical level. A possible approach to overcome these limitations is the encapsulation of curcumin into nano-carriers, incl. liposomes. The present contribution is focused on feasibility of using hybrid pH-sensitive liposomes, whereby curcumin is entrapped as a free drug and as a water soluble inclusion complex with PEGylated tert-butylcalix[4]arene, which allows the drug to occupy both the phospholipid membranes and the aqueous core of liposomes. The inclusion complexes were encapsulated in dipalmithoylphosphathydilcholine:cholesterol liposomes, whose membranes were grafted with a poly(isoprene-b-acrylic acid) diblock copolymer to confer pH-sensitivity. The liposomes were characterized by DLS, ζ-potential measurements, cryo-TEM, curcumin encapsulation efficacy, loading capacity, and in vitro release as a function of pH. Free and formulated curcumin were further investigated for cytotoxicity, apoptosis-induction and caspase-8, and 9 activation in chemosensitive HL-60 and its resistant sublines HL-60/Dox and HL-60/CDDP. Formulated curcumin was superior cytotoxic and apoptogenic agent vs. the free drug. The mechanistic assay demonstrated that the potent proapoptotic effects of pH-sensitive liposomal curcumin presumably mediated via recruitment of both extrinsic and intrinsic apoptotic pathways in both HL-60 and HL-60/CDDP cells