Analysis of Clinical Success and Molecular Mechanisms of Action of Novel Anti-glioblastoma Drugs: A Review.

Background: Gliomas and glioblastomas (GBM) are common primary malignant brain tumors, which are highly malignant and have a poor prognosis. The presence of cancer stem cells with unrestricted proliferative capacity and ability to generate glial neoplastic cells, the diffuse nature of GBM, and other specific factors of GBM contribute to poor results of drug therapy in patients with GBM. Despite the worldwide efforts to improve the treatment, many novel anti-GBM drugs are active just in vitro, in silico, and in preclinical trials, and they sometimes demonstrate poor or no activity in clinical trials.

Temozolomide Efficacy and Metabolism: The Implicit Relevance of Nanoscale Delivery Systems.

The most common primary malignant brain tumors in adults are gliomas. Glioblastoma is the most prevalent and aggressive tumor subtype of glioma. Current standards for the treatment of glioblastoma include a combination of surgical, radiation, and drug therapy methods.

Targeted Delivery Methods for Anticancer Drugs.

Several drug-delivery systems have been reported on and often successfully applied in cancer therapy. Cell-targeted delivery can reduce the overall toxicity of cytotoxic drugs and increase their effectiveness and selectivity. Besides traditional liposomal and micellar formulations, various nanocarrier systems have recently become the focus of developmental interest.

Gastroprotective effect of on ethanol-induced gastric mucosal injury: Histopathological evaluations.

Objective: Modern treatment of peptic ulcers includes antibacterial and gastroprotective medications. However, current anti-ulcer drugs possess severe side effects. Therefore, all attempts to find new effective medications free from side effects are justified.

PCSK9 as a Target for Development of a New Generation of Hypolipidemic Drugs.

PCSK9 has now become an important target to create new classes of lipid-lowering drugs. The prevention of its interaction with LDL receptors allows an increase in the number of these receptors on the surface of the cell membrane of hepatocytes, which leads to an increase in the uptake of cholesterol-rich atherogenic LDL from the bloodstream. The PCSK9 antagonists described in this review belong to different classes of compounds, may have a low molecular weight or belong to macromolecular structures, and also demonstrate different mechanisms of action.

Neuroprotective effect of poly(lactic-co-glycolic acid) nanoparticle-bound brain-derived neurotrophic factor in a permanent middle cerebral artery occlusion model of ischemia in rats.

Poly (lactide‑co‑glycolide) (PLGA) nanoparticles (NPs) are biodegradable carriers that participate in the transport of neuroprotective drugs across the blood brain barrier (BBB). Targeted brain‑derived neurotrophic factor (BDNF) delivery across the BBB could provide neuroprotection in brain injury. We tested the neuroprotective effect of PLGA nanoparticle‑bound BDNF in a permanent middle cerebral artery occlusion (pMCAO) model of ischemia in rats.

INTERCHANGEABILITY OF VIRAL VACCINES FOR IMMUNIZATION.

The review presents the results of the analysis of domestic and foreign scientific literature on the interchangeability of hepatitis A, B and influenza vaccines. The WHO materials, regulatory documents, data from scientific literature of foreign countries and Russia about the vaccine interchangeability are summarized. The problem of objective assessment of interchangeability of drugs is relevant worldwide.

Mechanism of the anticataract effect of liposomal MgT in galactose-fed rats.

Purpose: Increased lenticular oxidative stress and altered calcium/magnesium (Ca/Mg) homeostasis underlie cataractogenesis. We developed a liposomal formulation of magnesium taurate (MgT) and studied its effects on Ca/Mg homeostasis and lenticular oxidative and nitrosative stress in galactose-fed rats.

Methods: The galactose-fed rats were topically treated with liposomal MgT (LMgT), liposomal taurine (LTau), or corresponding vehicles twice daily for 28 days with weekly anterior segment imaging.

Brain-derived neurotrophic factor delivered to the brain using poly (lactide-co-glycolide) nanoparticles improves neurological and cognitive outcome in mice with traumatic brain injury.

Currently, traumatic brain injury (TBI) is the leading cause of death or disabilities in young individuals worldwide. The multi-complexity of its pathogenesis as well as impermeability of the blood-brain barrier (BBB) makes the drug choice and delivery very challenging. The brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity, neuronal cell growth, proliferation, cell survival and long-term memory.

A mouse model of weight-drop closed head injury: emphasis on cognitive and neurological deficiency.

Traumatic brain injury (TBI) is a leading cause of death and disability in individuals worldwide. Producing a clinically relevant TBI model in small-sized animals remains fairly challenging. For good screening of potential therapeutics, which are effective in the treatment of TBI, animal models of TBI should be established and standardized.

Safety and efficacy of valproic acid preparations.

Background: Rising of the cost of drug therapy is one of the most notable negative tendencies of modern medicine. The main reasons for this trend are the increased costs for preclinical and clinical phases of drug development. Reproduction of drugs after cessation of patent protection is much less costly.

Intraocular distribution of topically applied hydrophilic and lipophilic substances in rat eyes.

Purpose: Topical administration is the preferred route of drug delivery for ophthalmic ailments. However, poor permeation through ocular surface and significant systemic absorption, makes the topical drug delivery challenging. Furthermore, distribution of topically delivered drugs varies with their physicochemical properties and the type of formulation used.

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness.

Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF) has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood-retinal barrier and blood-cochlear barrier, which have a comparable structure to the blood-brain barrier prevent molecules of larger sizes (such as BDNF) from exiting the circulation and reaching the targeted cells.

Liposomes in topical ophthalmic drug delivery: an update.

Topical route of administration is the most commonly used method for the treatment of ophthalmic diseases. However, presence of several layers of permeation barriers starting from the tear film till the inner layers of cornea make it difficult to achieve the therapeutic concentrations in the target tissue within the eye. In order to circumvent these barriers and to provide sustained and targeted drug delivery, tremendous advances have been made in developing efficient and safe drug delivery systems.

Effects of topically applied tocotrienol on cataractogenesis and lens redox status in galactosemic rats.

Purpose: Oxidative and nitrosative stress underlies cataractogenesis, and therefore, various antioxidants have been investigated for anticataract properties. Several vitamin E analogs have also been studied for anticataract effects due to their antioxidant properties; however, the anticataract properties of tocotrienols have not been investigated. In this study, we investigated the effects of topically applied tocotrienol on the onset and progression of cataract and lenticular oxidative and nitrosative stress in galactosemic rats.

Nanoscale drug delivery systems and the blood-brain barrier.

The protective properties of the blood-brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain's vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual's age.

The tissue-specific "ferromagnetic attack" on hyperactivation of ATP synthesis by magnesium-25 in mitochondria.

A (25)Mg(2+)-operated hyper-activation of ATP synthesis has been investigated in mitochondria (Mt) isolated from iron-rich and iron-poor rat tissues: spleen, liver, skeletal muscle, myocardium, kidneys, brain. Both magnetic ((25)Mg) and non-magnetic ((24)Mg) magnesium isotopes were separately administered to estimate the degree of the ATP production related to the magnetic isotope effect (MIE) of (25)Mg(2+)as a function of the amount of Mt-endogenous iron ions. A strong but negative (r = -0.

Cytotoxic effect of paclitaxel incorporated in nanoparticles based on lactic and glycolic acid copolymer.

Paclitaxel dosage form on nanoparticles of 200-300 nm based on lactic and glycolic acid copolymer was obtained by the co-precipitation method. The possibility of controlled release of paclitaxel at pH 7.4 for 24 h was studied in vitro.

Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles.

The nerve growth factor (NGF) is essential for the survival of both peripheral ganglion cells and central cholinergic neurons in the basal forebrain. The accelerated loss of central cholinergic neurons during Alzheimer's disease may be a determinant cause of dementia, and this observation may suggest a possible therapeutic benefit from treatment with NGF. In recent years, convincing data have been published involving neurotrophic factors for the modulation of dopaminergic transmission within the brain and concerning the ability of NGF to prevent the degeneration of dopaminergic neurons.

Antiparkinsonian effect of nerve growth factor adsorbed on polybutylcyanoacrylate nanoparticles coated with polysorbate-80.

The study examined the antiparkinsonian effect of nerve growth factor adsorbed on the surface of polybutylcyanoacrylate nanoparticles coated with polysorbate-80 surfactant. The parkinsonian syndrome in C57B1/6 mice was provoked by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The basic symptoms of the parkinsonian syndrome decreased under the action of the nerve growth factor adsorbed on nanoparticles coated with polysorbate-80, which was seen from decreased rigidity and increased locomotor activity compared to control mice receiving with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine alone.

The porphyrin-fullerene nanoparticles to promote the ATP overproduction in myocardium: 25Mg2+-magnetic isotope effect.

This is a first case ever reported on the fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) designed for targeted delivery of the paramagnetic magnesium stable isotope to the heart muscle providing a sharp clinical effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 h after a single injection (0.03-0.1 LD(50)).

Fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) to treat hypoxia-induced mitochondrial dysfunction in mammalian heart muscle.

Background: This is the first report on the targeted delivery of fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) to treat hypoxia-induced mitochondrial dysfunction in mammalian heart muscle.

Methods: The magnetic isotope effect generated by the release of paramagnetic (25)Mg(2+) from these nanoparticles selectively stimulates the ATP overproduction in the oxygen-depleted cell.

Results: Because nanoparticles are membranotropic cationites, they will only release the overactivating paramagnetic cations in response to hypoxia-induced acidic shift.

Effects of apolipoproteins on dalargin transport across the blood-brain barrier.

Antinociceptive activity of dalargin (7.5 mg/kg) adsorbed on poly(butyl)cyanoacrylate nanoparticles with different coating was studied on outbred albino mice by the tail-flick test. poly(butyl)cyanoacrylate nanoparticles without coating did not increase the antinociceptive activity of dalargin and hence, did not increase its transport across the blood-brain barrier.

Covalent linkage of apolipoprotein e to albumin nanoparticles strongly enhances drug transport into the brain.

Drug delivery to the brain is becoming more and more important but is severely restricted by the blood-brain barrier. Nanoparticles coated with polysorbates have previously been shown to enable the transport of several drugs across the blood-brain barrier, which under normal circumstances is impermeable to these compounds. Apolipoprotein E was suggested to mediate this drug transport across the blood-brain barrier.