Virginia Tzankova

Recently, the probiotics' therapeutic influence on different hepatic disorders has been established. Given the fact that free radicals are involved in the toxic liver injury pathogenesis, it was important to investigate whether the probiotic cocktail LDB-ST could be used as an antioxidant and a hepatoprotective agent. The antioxidant and hepatoprot...

The topical administration of in situ hydrogels for ocular pathologies is a promising application strategy for providing high effectiveness and patient compliance. Curcumin, a natural polyphenol, possesses all the prerequisites for successful therapy of ophthalmic diseases, but unfortunately its physicochemical properties hurdle the practical use....

The study investigates the development and characterization of dual-loaded niosomes incorporated into ion-sensitive in situ gel as a potential drug delivery platform for ophthalmic application. Cannabidiol (CBD) and epigallocatechin-3-gallate (EGCG) simultaneously loaded niosomes were prepared via the thin film hydration (TFH) method followed by pu...

The simultaneous encapsulation of drugs into nanosized delivery systems could be beneficial for cancer therapies since it could alleviate adverse reactions as well as provide synergistic effects. However, the encapsulation of hydrophobic drugs into hydrophilic nanoparticles, such as nanogels, could be challenging. Therefore, innovative technologica...

Triterpenoid saponins from the Astragalus species possess valuable effects (cytotoxic, adjuvant, hepatoprotective, neuroprotective, antiviral, etc.). Some also have immunomodulatory activities. Astragalus glycyphyllos is distributed in Bulgaria and mainly accumulates cycloartane saponins. From the overground parts of the species, a triterpenoid cyl...

Neurodegenerative diseases such as Parkinson’s and Alzheimer’s continue to be some of the most significant challenges in modern medicine. Recent research related to the molecular mechanisms of parkinsonism has opened up new approaches to antiparkinsonian therapy. In response to this, we present the evaluation of the potential neuroprotective and MA...

The therapeutic approach to many solid tumors, including non-small cell lung cancer (NSCLC), is mainly based on the use of platinum-containing anticancer agents and is often characterized by acquired or intrinsic resistance to the drug. Therefore, the search for safer and more effective drugs is still an open challenge. Two organometallic rutheniu...

Resveratrol could be applied in wound healing therapies because of its antioxidant, anti-inflammatory and antibacterial effects. However, the main limitation of resveratrol is its low aqueous solubility. In this study, resveratrol was included in hydroxypropyl-β-cyclodextrin complexes and further formulated in Pluronic F-127 hydrogels for wound tre...

Considering the complex pathogenesis of Alzheimer’s disease (AD), the multitarget ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target approach. Thus, a series of 13 novel (5e-q) pyrrole-based Schiff bases were synthesized by conventional and microwave-assisted c...

Agar, a naturally occurring polysaccharide, has been modified by grafting it with acrylic (AcA) and methacrylic (McA) acid monomers, resulting in acrylic or methacrylic acid grafted polymer (AA-g-AcA or AA-g-McA) with pH-sensitive swelling behavior. Different ratios between agar, monomers, and initiator were applied. The synthesized grades of both...

Budesonide is a mineral corticoid applied in the local therapy of pediatric atopic dermatitis. Unfortunately, its dermal administration is hindered by the concomitant adverse effects and its physicochemical properties. The characteristic pH change in the atopic lesions can be utilized for the preparation of a pH-sensitive nanocarrier. In this view,...

Hydrogels can offer many opportunities for drug delivery strategies. They can be used on their own, or their benefits can be further exploited in combination with other nanocarriers. Intelligent hydrogels that react to changes in the surrounding environment can be utilized as gatekeepers and provide sustained on-demand drug release. In this study,...

Hydrogels can offer many opportunities for drug delivery strategies. They can be used on their own or their benefits can be further exploited in combination with other nanocarriers. Intelligent hydrogels that react to changes in the surrounding environment can be utilized as gatekeepers and provide sustained on demand drug release. In this study, a...

A series of ten new hydrazide–hydrazone derivatives bearing a pyrrole ring were synthesized and structurally elucidated through appropriate spectral characteristics. The target hydrazones were assessed for radical scavenging activity through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) test...

Alzheimer’s disease (AD) is considered a complex neurodegenerative condition which warrants the development of multitargeted drugs to tackle the key pathogenetic mechanisms of the disease. In this study, two novel series of melatonin- and donepezil-based hybrid molecules with hydrazone (3a–r) or sulfonyl hydrazone (5a–l) fragments were designed, sy...

Quercetin is a flavonoid with high antioxidant activity, and thus it is an appropriate candidate for incorporation in dermal dosage forms. Unfortunately, the limited skin penetration, low water solubility and chemical instability of quercetin make it typically difficult for incorporation in sustained-release dermal and transdermal drug formulations...

Nanogels are attractive drug delivery systems that provide high loading capacity for drug molecules, improve their stability, and increase cellular uptake. Natural antioxidants, especially polyphenols such as resveratrol, are distinguished by low aqueous solubility, which hinders therapeutic activity. Thus, in the present study, resveratrol was inc...

Background: One of the therapeutic limitations of the use of doxorubicin (DOX) as an anticancer drug is its cardiotoxicity. Its hydrophilicity also causes difficulties in achieving sustained release. The simultaneous delivery with the well-known natural antioxidant quercetin could ameliorate its cardiotoxicity. Thus, the main aim of this work is to...

The anthracycline antibiotic doxorubicin is a well-known antitumour agent, however its cardiotoxicity is a significant obstacle to therapy. The aim of the present study was to improve the safety of doxorubicin through its simultaneous encapsulation with a cardioprotective agent (resveratrol) in Pluronic micelles. The formation and double-loading of...

Parkinson’s disease is a huge burden in modern medicinal practice. A serious drawback of current antiparkinsonian therapy is its symptomatic nature. This directed our investigations in the search for new more potent derivatives, affecting not only the loss of dopaminergic neurons but also the oxidative damage of neuronal cells. Thus in vitro neurot...

The present study is focused on the development of cannabidiol-loaded polymeric nanomicelles as a drug delivery system with neuroprotective effects. Cannabidiol was loaded in Pluronic micelles (Pluronic P123 or its combination with Pluronic F127) possessing an average diameter smaller than 50 nm and high encapsulation efficiency for the hydrophobic...

Four pyrrole based hydazide-hydrazones with established low hepatotoxicity and promising antiproliferative activity were evaluated (at 1µM concentration) for possible inhibitory activity on human isoforms of Cytochrome P450 CYP1A2, CYP3A4 and CYP2D6. The compounds didn’t exert any statistically significant inhibitory effects on CYP1A2 and CYP2D6. H...

Thermo-responsive copolymer, Agar agar-graft-poly(N-vinylcaproactam) (AA-g-PnVCL) was prepared by grafting N-vinylcaprolactam units onto the Agar backbone. Graft copolymer was synthesized by free-radical polymerization, using 2,2′-Azobis(2,4-dimethylvaleronitrile) (AMVN) as an initiator in the nitrogen atmosphere. In order to evaluate the compositi...

Background The significant increase of patients suffering from different types of cancer, guides scientists to take prompt measures in the development of novel and effective antiproliferative agents, where the intercalation of heterocyclic fragment in the designed molecules has proven to be a useful practice. Objective The newly synthesized compou...

Background Caffeic acid phenethyl ester (CAPE) (a component of honey bee propolis) possesses various biological activities. However, the high lipophilicity of CAPE limits its applications, since it hinders both the formulation of stable drug dosage forms and its bioavailability. In attempt to overcome these problems, CAPE was loaded in micelles bas...

Oxidative stress is a key contributing factor in the complex degenerating cascade in Parkinson’s disease. The inhibition of MAO-B affords higher dopamine bioavailability and stops ROS formation. The incorporation of hydroxy and methoxy groups in the arylhydrazone moiety of a new series of 1,3-disubstituted benzimidazole-2-thiones could increase the...

Sdox is a hydrogen sulfide (H2S)-releasing doxorubicin effective in P-glycoprotein-overexpressing/doxorubicin-resistant tumor models and not cytotoxic, as the parental drug, in H9c2 cardiomyocytes. The aim of this study was the assessment of Sdox drug-like features and its absorption, distribution, metabolism, and excretion (ADME)/toxicity properti...

The paper is focused on safety evaluation, antioxidant activity and neuroprotective properties determination of newly synthesized substituted N-pyrrolyl hydrazide hydrazones on two neuronal in vitro models: human neuronal cells SH-SY5Y and isolated rat brain synaptosomes. Preliminary toxicological data indicated low or no in vitro toxicity for all...

Antioxidant capacity of poorly soluble natural antioxidant kaempferol, in particular free or loaded in two types of cationic micelles, was studied on non-enzyme induced lipid peroxidation (LPO) in vitro . The micelles were based on triblock copolymers - poly(2-(dimethylamino)ethyl methacrylate-b-poly(propylene oxide)-b-poly(2-(dimethylamino)ethyl m...

Neuroprotective drugs and selective monoamine oxidase inhibitors can slow down the progression and improve symptoms of Parkinson’s disease (PD). Since there is an implication of oxidative stress in the pathophysiological mechanisms of the disease, the compounds possessing an ability to reduce the oxidative stress are prime candidates for neuroprote...

A modified UHPLC-HRMS method for simultaneous quantification of eight flavonoids from the aerial parts of the wild spinach ( Chenopodium bonus-henricus L.) was re-validated for specificity, the limit of detection and quantitation limit, linearity, accuracy, and precision. The glycosides of spinacetin ( Chbhnf-04, Chbhnf-06 , and Chbhnf-08 ) and pat...

Triterpenoids are well known metabolic syndrome (MetS) modulators. One of the suggested molecular mechanisms of action involves peroxisome proliferator-activated receptor gamma (PPARγ) activation. In this study we aimed to: (i) develop a virtual screening (VS) protocol for PPARγ weak partial agonists, (ii) predict potential metabolic transformation...

This study presents the potential of Mobil Composition of Matter No.41 (MCM-41) and Hollow Mesoporous Silica (HMS) as an efficient drug delivery system for anticancer drug bicalutamide (BLT). Bicalutamide loaded nanoparticles were characterized by using X-ray diffraction (XRD), N2-physisorption, dynamic light scattering (DLS), TEM and attenuated to...

Many species of genus Astragalus have been extensively studied for their wide range of biological activities, including antioxidant, cytoprotective, anti-inflammatory, antitumour, anti-infective, immune-boosting, antihypertensive and antidiabetic effects. This study presents an in vitro evaluation of the anticancer and immunomodulating properties o...

Multifunctional nanocarriers of two or more anticancer drugs with different pharmacological mechanisms are being developed for combination therapy, which aims at achieving synergistic effects in cancer treatment and overcoming the increasingly common problem of drug resistance. This contribution reports the fabrication of functional nanosized micel...

Abstarct A synthetic strategy towards modular polymer platform capable of further tunable degree of modification is presented. Initially, a well-defined amphiphilic block copolymer with alkyne side groups distributed along the biodegradable hydrophobic block was successfully prepared applying controlled ring-opening copolymerization of D,L-lactide...

Caffeic acid phenethyl ester (CAPE), a major pharmacologically active component of poplar type propolis, is known for its proapoptotic, anti-inflammatory, antioxidant, antiviral, and enzyme inhibiting activities. The aim of this study was to perform an in vitro and in vivo safety assessment of a micellar system based on a newly synthesized copolyme...

The present study evaluated the impact of doxorubicin encapsulation in chitosan-alginate nanoparticles on its stability, cytotoxic potential in multidrug resistant lymphoma cells (L5178 MDR1) and toxicity in H9c2 cardioblasts. The results indicated that the encapsulation stabilized the drug against degradation due to its inner location in nanoparti...

Background Many neurodegenerative disorders include oxidative stress-mediated pathology. Melatonin and its metabolites act as endogenous reactive oxygen species (ROS) scavengers and antioxidants. N,N′-Disubstituted benzimidazole-2-thiones with extended side chains could exert antioxidant and neuroprotective properties due to structural similarities...

The effects of new derivatives of caffeine-8-thioglycolic acid (100 µM) on isolated rat brain synaptosomes, human neuroblastoma cell line SH-SY5Y and human recombinant MAOB enzyme (hMAOB) (1 µM) were evaluated. Most of the compounds, administered alone, didn’t show statistically significant neurotoxic effects on SH-SY5Y, when compared to the contro...

In this work series new theobromine derivatives containing an arylpiperazine moiety at N 1 with established antioxidant and antiproliferative activities were evaluated for their hepatotoxic effects on cellular and sub-cellular level. On isolated rat hepatocytes, 3c and 4c expressed lowest toxicity, while 3f and 4f showed highest toxicity. The same...

The natural bioactive compound caffeic acid phenethyl ester (CAPE) possesses antioxidant, antiinflammatory and anticancer activity. However, the in vivo application of CAPE is limited due to its poor solubility in aqueous media. In this contribution, we report a strategy for enhancing the solubility of CAPE in water by novel micellar carriers compr...

Amphiphilic diblock copolymers consisting of hydrophilic polyglycidol (PG) and hydrophobic poly(allylglycidyl ether) (PAGE) were prepared by sequential anionic ring‐opening polymerization of allylglycidyl ether and ethoxyethyl glycidyl ether followed by removal of the protective ethoxyethyl groups. The polymerization was initiated by partially depr...

Oxidative stress is related to the pathogenesis of many neurodegenerative disorders, including [...]

In this study, spherical hollow mesoporous silica (HMS) particles with average size of 550 nm were loaded with dopamine-receptor agonist pramipexole, as a model drug. High drug loading (55%) was achieved by its incorporation in the reservoir structure of HMS. The newly developed drug-delivery systems were further double-coated with bioadhesive poly...

Muscimol is the main compound found in Amanita muscaria. Several studies have proven that muscimol has suppressive effects on essential tremor, without impairing speech and coordination. The effects of muscimol in Parkinson-affected patients is also described in a number of studies. These studies describe the free radical scavenging and antioxidant...

Objective: The syntheses and biological activities of 8-thiosubstituted-1,3,7- trimethylxanthine derivatives bearing an aromatic hydrazide-hydrazone fragment in the side chain at C8 are described. Methods: The chemical structures of the synthesized compounds 6a-m were confirmed based on their MS, FTIR, 1H NMR and 13C NMR analyses. Results: The...

The present study reports a promising antioxidant protection by a recently developed micellar propolis formulation, against oxidative stress in in vitro and in vivo models of toxicity. The formulation, based on poplar propolis encapsulated in poly(ethylene oxide)–b-poly(propylene oxide)–b-poly(ethylene oxide) triblock copolymer (PEO26–PPO40–PEO26)...

Lomefloxacin (LF) is interesting as a model molecule from a safety point of view because of its high potential for serious adverse drug effects (i.e. phototoxic reactions). In this study, MCM-41 mesoporous silica nanoparticles (MCM-41) were loaded with lomefloxacin, aiming to overcome the drug’s intrinsic cytotoxicity. The good biocompatibility of...

Herein, we present development of new pH-responsive drug delivery systems for D3-dopamine receptor agonist pramipexole, based on its encapsulation in MCM-41 mesoporous silica particles. Pramipexole loaded particles were further coated with chitosan and/or sodium alginate in order to modify drug release. The prepared pramipexole loaded nanoparticles...

This studyinvestigates the effects of newly synthetized derivatives of caffeine-8 thioglycolic acid on isolated rat liver microsomes. The microsomeswere received by multiple centrifugation. The production of malondialdehyde (MDA) was exam as a marker of lipid peroxidation. The effects were compared to those of caffeine. From all exam compounds, onl...

Caffeic acid phenethyl ester (CAPE), a hydrophobic constituent of poplar propolis of valuable biological activity, was immobilized in poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-b-PCL-b-PEO) copolymer micelles to improve its solubility in water. CAPE was loaded in the micelles by dialysis, achieving ca. 50% encapsulation...

Parkinson's disease (PD) is a neurodegenerative and debilitating disease that affects 1% of elderly population. Patient's motor disability results in an extreme difficulty to deal with daily activities. Conventional treatment is limited to dopamine replacement therapy, which fails to delay disease's progression and is often associated with a number...

In this study the co-assembly of two amphiphilic block copolymers with tailored composition and molecular characteristics, poly(ethylene oxide)-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO113-b-PCL35-b-PEO113) and poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA20-b-PCL70-b-PD...

Crosslinked carriers based on cationic monomer [2-(acryloyloxy)ethyl]trimethylammonium chloride or 2-(dimethylamino)ethyl methacrylate were developed and investigated as new platform for ibuprofen transdermal delivery. Series of networks of varied composition and structure were synthesized and characterized by FTIR spectroscopy and following swelli...

New series of N,N′-disubstituted benzimidazole-2-thione were synthesized by introduction of hydrazone moiety in the side chains. The toxicological potential of studied compounds was evaluated by monitoring the cell viability and levels of lactate dehydrogenase, glutathione and malonaldehyde in isolated rat hepatocytes. The antioxidant properties of...

Nanomedicine and nanopharmacy are relatively new and promising branches of medical science. They apply specific approaches for overcoming therapy limitations such as: low selectivity, impermeability of biological membranes, unfavorable physicochemical properties and pharmacokinetics of drugs. Nanomedicines are systems with finely controlled charact...

Nanotoxicology evaluates the relationship between the structure properties of nanoparticles and toxic hazard, which is of considerable importance prior to clinical application of nanosystems. In spite of the introduction of nanotoxicology in regulatory affairs and the elucidation of some physicochemical structure - toxicity relationships by means o...

The aim of the present study was to evaluate the protective effects of free and encapsulated quercetin against oxidative stress injury in neuronal SH-SY5Y cells and isolated rat brain synaptosomes. Quercetin (QR) was encapsulated in nanoparticles consisting of sodium alginate and chitosan and the ratio between both biopolymers was 10:1 or 1:10, res...

The toxic liver impairment caused by free radical injury or excessive reactive oxigen species (ROS) formation could be effectivelly attenuated by natural antioxidants. The present study aimed to explore and compare the hepatoprotective and antioxidant effects of free and encapsulated quercetin in in vitro and in vivo models of hepatotoxicity. Thus,...

The present study deals with development and evaluation of the safety profile of chitosan/alginate nanoparticles as a platform for delivery of a natural antioxidant quercetin. The nanoparticles were prepared by varying the ratios between both biopolymers giving different size and charge of the formulations. The biocompatibility was explored in vitr...

Multifunctional nanocarriers are gaining increasing research interest as polymeric platforms for targeted drug delivery in cancer therapy and diagnosis. In this work, preparation and characterization of surfactant-free polyester nanoparticles (NPs) from a bio-based poly (butylene sebacate-co-butylene dilinoleate)s, PBSE/PBDL, using nanoprecipitatio...

Three new flavonoid glycosides (7–9) named patuletin-3-O-(5″″-О-Е-feruloyl)-β-d-apiofuranosyl(1 → 2)[β-d-glucopyranosyl (1 → 6)]-β-d-glucopyranoside (7), spinacetin-3-O-(5″″-О-Е-feruloyl)-β-d-apiofuranosyl (1 → 2)[β-d-glucopyranosyl(1 → 6)]-β-d-glucopyranoside (8) and 6-methoxykaempferol-3-O-(5″″-О-Е-feruloyl)-β-d-apiofuranosyl(1 → 2)[β-d-glucopyra...

To evaluate the safety profile of cationic micelles, based on triblock copolymer poly(dimethylaminoethyl methacrylate) - poly(e-caprolactone) - poly(dimethylaminoethyl methacrylate) (PDMAEMA9-PCL70-PDMAEMA9), the effects of empty (PM) and curcumin loaded micelles (PM-Curc) on nonenzyme induced lipid peroxidation (LPO) in vitro, hemolytic activity a...

A new method for the synthesis of 1,3-disubstituted benzimidazole derivatives was developed using aza-Michael addition. The target compounds were synthesized in good yields and purity and tested on isolated hepatocytes for their toxicity and antioxidant activity. The antioxidant properties of the substances with lowest toxicity were evaluated using...

The numerous beneficial pharmacological properties of quercetin justify its future clinical application. Nevertheless, the use of quercetin as a safe and effective therapeutic agent in the treatment of various diseases is limited because of the poor water solubility and membrane permeability, low bioavailability and instability. Several approaches...

The present study aims to explore the protective effects of pramipexol loaded in mesoporous silica particles in a model of oxidative stress damage in human neuroblastoma SH-SY5Y cells in vitro. Pramipexol is a dopamine agonist which is applied for the treatment of early and advanced Parkinson's disease. Mesoporous silica nanoparticles are attractiv...

Curcumin is a polyphenolic substance with attractive pharmacological activities (e.g. antioxidant, anti-inflammatory, anticancer). Incorporation of curcumin in polymeric micelles could overcome the problems associated with its instability and low aqueous solubility. The aim of this study was to load curcumin in polymeric micelles based on Pluronic®...

One of the main approaches to increase the therapeutic effectiveness of the controlled drug delivery systems is the development of new polymeric carriers designed to match the specific properties of a given drug molecule. In present paper properties of a newly synthesized polymer network based on cationic poly{[2-(acryloyloxy)ethyl]-trimethylammoni...

The effects of new derivatives of caffeine-8-thioglycolic acid with proven antihypoxic activity were investigated in this study. The compounds were eval- uated for possible cytotoxic effects on isolated rat hepatocytes, isolated by two-stepped, collagenase perfusion. As biomarkers of cytotoxicity we measured cell viability by trypan blue exclusion,...

The development of matrices to control the release of drugs into specific sites in the human body is a perspective biomedical application of polymeric materials. The aim of this work was to evaluate the cytotoxicity of a newly synthesized functional block copolymer of composition PEO-b-PDMA for application in nanosized drug delivery systems. The to...

Nanomaterials provide great potential of commercial benefits but some of them have been claimed to be toxic in in vivo and in vitro tests. Although different nanomaterials have been assessed and proposed as drug-delivery carriers, information on possible mechanisms of their toxicity is insufficient. The liver is the target organ after oral, intrave...

The use of nanoscale biomaterials as drug delivery systems has been exponentially growing in the recent years. Various functional biocompatible drug nanocarriers were designed in order to avoid some problems like low solubility, low bioavailability, and extended biotransformation etc. Among the carriers, mesoporous silica materials and polymeric na...

A new series of N-substituted 1-benzyltheobromine-8-thioacetamides were designed and synthesized. Their anti-proliferative activity against human chronic myelocytic leukemia cell K562, human T-cell leukemia cell SKW-3 and human acute myeloid leukemia HL-60 was evaluated. For the tested compounds a concentration-dependent cytotoxic activity was obse...

One new, namely 6-methoxykaempferol 3-O-[β-apiofuranosyl(1→2)]-β-glucopyranosyl(1→6)-β-glucopyranoside (2), and two known flavonoid glycosides, spinacetin 3-O-[β-apiofuranosyl(1→2)]-β-glucopyranosyl(1→6)-β-glucopyranoside (1) and spinacetin 3-O-gentiobioside (3), were isolated from the roots of Chenopodium bonus-henricus L. Their structures were de...

The potential of poly(methyl methacrylate-co-acrylic acid) (PMMA-AA) copolymers to form hollow particles and their further formulation as curcumin delivery system have been explored. The particles were functionalized by crosslinking the acrylic acid groups via bis-amide formation with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazid...

One new, namely 6-methoxykaempferol 3-O-[β-apiofuranosyl(1→2)]-β-glucopyranosyl(1→6)-β-glucopyranoside (2), and two known flavonoid glycosides, spinacetin 3-O-[β-apiofuranosyl(1→2)]-β-glucopyranosyl(1→6)-β-glucopyranoside (1) and spinacetin 3-O-gentiobioside (3), were isolated from the roots of Chenopodium bonus-henricus L. Their structures were de...

Four new 7,8-disubstituted theophylline derivartives were synthesized. Their purity was elucidated with melting points and TLC characteristics. The structure of the obtained compounds was proven by IR, 1H NMR and 13C NMR spectral data. The cytotoxicity, the in vitro effects on sub-cellular and cellular level and the antiproliferative activity of th...