ABSTRACT
The neuroprotective activity of recombinant human erythropoietin (rhEPO) loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been observed in rats with model intracerebral post-traumatic hematoma (hemorrhagic stroke). It is established that rhEPO-loaded PLGA nanoparticles produce a neuroprotective effect in rats with hemorrhagic stroke, which is manifested by reduced number of lethal outcomes and animals with neurological disorders. Treatment with rhEPO-loaded PLGA prevented amnesia of passive avoidance reflex (PAR), which was produced by the hemorrhagic stroke, and reduced the area of brain damage caused by the intracerebral hematoma. These effects were recorded during one-week observation period. Native rhEPO exhibited a similar, but much less pronounced effect on the major disorders caused by the model hemorrhagic stroke in rats.
Subject(s)
Amnesia/prevention & control , Cerebral Hemorrhage, Traumatic/drug therapy , Erythropoietin/therapeutic use , Neuroprotective Agents/therapeutic use , Animals , Avoidance Learning/drug effects , Cerebral Hemorrhage, Traumatic/mortality , Cerebral Hemorrhage, Traumatic/physiopathology , Disease Models, Animal , Drug Carriers/chemistry , Erythropoietin/administration & dosage , Humans , Lactic Acid/chemistry , Male , Nanoparticles/chemistry , Neuroprotective Agents/administration & dosage , Particle Size , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Rats , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Survival RateABSTRACT
Paclitaxel-loaded poly(lactic-glycolic) copolymer nanoparticles have been prepared using a precipitation technique. The cytotoxic activity of nanosomal paclitaxel was studied on the model of highly resistant cell line Jurkat WT (human T-cell leukemia) using various biochemical assays. It is found that the inhibitory concentration (IC50) for the experimental formulation of paclitaxel falls within 10(-4)-10(-6) M. Accumulation of nanoparticles in the highly resistant Jurkat/WT cells was revealed by fluorescence microscopy.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Drug Resistance, Neoplasm/drug effects , Leukemia, T-Cell/drug therapy , Nanoparticles , Paclitaxel/pharmacology , Drug Screening Assays, Antitumor , Humans , Jurkat Cells , Leukemia, T-Cell/pathologyABSTRACT
The neuroprotective activity of recombinant human erythropoietin (r-HuEpo) sorbed on poly(butyl)cyanoacrilate nanoparticles (EPO-PBCA) and on polylactic-co-glycolic acid nanoparticles (EPO-PLGA) has been studied on Wistar rats with intracerebral post-traumatic hematoma (model of hemorrhagic stroke) (IPH-HS) in comparison to native r-HuEpo. It is established that EPO-PBCA produced a protective effect in rats after IPH-HS that was manifested by a decrease in the number of animals with neurological disorders such as circus movement, paresis, and paralysis of hind limbs; the drug also improved coordination (rotating rod test), reduced the number of lost animals, and decreased the loss weight among survived rats. In addition, EPO-PBCA optimized the research behavior of rats with IPH-HS in the open field test and prevented amnesia of passive avoidance reflex (PAR), which was caused by the IPH-HS. These effects were manifested during a two-week observation period. EPO-PLGA has a similar but much less pronounced effect on the major disorders caused by IPH-HS. The efficiency of native r-HuEpo as a neuropotective agent was insignificant and only manifested by decrease in the number of lost animals with IPH-HS.
Subject(s)
Cerebral Hemorrhage/drug therapy , Erythropoietin/administration & dosage , Nanoparticles/chemistry , Neuroprotective Agents/administration & dosage , Recombinant Proteins/administration & dosage , Stroke/drug therapy , Adsorption , Amnesia/drug therapy , Amnesia/prevention & control , Animals , Cerebral Hemorrhage/mortality , Cerebral Hemorrhage/physiopathology , Cerebral Hemorrhage/psychology , Disease Models, Animal , Enbucrilate/chemistry , Erythropoietin/chemistry , Erythropoietin/therapeutic use , Humans , Lactic Acid/chemistry , Male , Motor Activity/drug effects , Neuroprotective Agents/chemistry , Neuroprotective Agents/therapeutic use , Paralysis/drug therapy , Paralysis/prevention & control , Paresis/drug therapy , Paresis/prevention & control , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Rats , Rats, Wistar , Recombinant Proteins/chemistry , Recombinant Proteins/therapeutic use , Stroke/mortality , Stroke/physiopathology , Stroke/psychology , Survival Rate , Weight Loss/drug effectsABSTRACT
Estradiol, ethynylestradiol, and estradiol acetate possess antiradical activity (K7 = (1.8-2.0) x 10(-4) liter/mole sec). Nistranol exhibits antiradical properties only upon acid hydrolysis. The results of experiments with egg yolk liposomes showed evidence of a pronounced antioxidant activity of estradiol, ethynylestradiol, and estradiol nitrate, and the absence of such activity in nistranol. In the experiments on rat heart homogenates, nitroestrogens in a concentration of about 10(-4) M reduced the level of TBA-active products.