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

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

In Vitro Evaluation of a Stable Monomeric Gold(II) Complex with Hematoporphyrin IX: Cytotoxicity against Tumor and Kidney Cells, Cellular Accumulation, and Induction of Apoptosis

The antineoplastic potential of a stable monomeric Au(II) complex with hematoporphyrin IX (Hp), namely [Au(II)Hp−2H.(H2O)2], was investigated in a panel of tumor cell lines. The complex exhibits strong cytotoxicity, whereby the leukaemia- and lymphoma-derived cell lines are more sensitive, with IC50 values comparable to those of the reference anticancer drug cisplatin. In contrast, the solid tumor models are more sensitive to the platinum drug. A comparative assessment of both agents against the human kidney cell line 293T has shown that [Au(II)Hp−2H.(H2O)2] is less cytotoxic. The gold complex induces oligonucleosomal DNA fragmentation in tumour cells following 24-hour treatment and hence its cytotoxic effect is at least partly mediated by induction of apoptotic cell death. A prominent intracellular gold accumulation was detected after treating tumor cells with [Au(II)Hp−2H.(H2O)2] which shows that its putative pharmacological targets are readily accessible after a short incubation period

Poly (ethylene oxide)-block-poly (n-butyl acrylate)-blockpoly (acrylic acid) triblock terpolymers with highly asymmetric hydrophilic blocks: synthesis and aqueous solution properties

The synthesis and aggregation behaviour in aqueous media of novel amphiphilic poly(ethylene oxide)- block-poly(n-butyl acrylate)-block-poly(acrylic acid) (PEO–PnBA–PAA) triblock terpolymers were studied. Terpolymers composed of two highly asymmetric hydrophilic PEO (113 monomer units) and PAA (10–17 units) blocks, and a longer soft hydrophobic PnBA block (163 or 223 units) were synthesized by atom transfer radical polymerisation (ATRP) of n-butyl acrylate and tert-butyl acrylate (tBA), followed by selective hydrolysis of the PtBA blocks. These terpolymers are not directly soluble in water but form defined spherical micelles by employing the dialysis method as confirmed by dynamic light scattering (DLS) and cryogenic transmission microscopy (cryo-TEM). Based on terpolymer architecture and composition, a three-layered micellar structure comprising a PnBA core, a PEO/PAA middle layer, and a PEO outer layer is suggested. The micelles do not dissociate to very low concentrations and, therefore, are promising candidates for long-circulating drug delivery systems. Further, as evidenced by high-performance liquid chromatography (HPLC), the micelles can load and release, without burst effect, the hydrophobic drug paclitaxel

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

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

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