betadex and Epilepsy

Neuropeptide Y (NPY) is a polypeptide sequence useful in regulating physiological functions like homeostasis, feeding, etc., but its usage is restricted due to its short half-life. β-cyclodextrin-crosslinked nanosponges improve the drug release and stability due to its wide cavity, which is helpful to deliver therapeutics. The present work aimed to formulate synthetic NPY-based nanocarriers as sponges by polymer condensation mechanism using design experiment to improve the peptide release and stability. The validated nanosponges exhibited a particle size of 423.42 ± 5.32 nm, 75.82 ± 7.43 % entrapment efficiency and 83.50 ± 6.54 % NPY release for 24 h. The NPY and β-cyclodextrin interaction was confirmed by X-ray diffraction, Fourier transform infrared and nuclear magnetic resonance spectroscopy. The NPY-loaded nanosponges were found stable for 6 months at two conditions (5 ± 2 °C and 25 ± 2 °C). The cross-linked nanocarriers of synthetic peptide-based nanosponges powder at different doses were administered intranasally using a metered-dose inhaler in the animal model to check its antiepileptic activity. The synthetic NPY-loaded nanosponges at higher doses showed significant antiepileptic effects equivalent to the standard drug (administered orally) in maximal electroshock and chemically-induced seizures with an increase of NPY in the brain directly proportional to GABAergic signalling by increase in GABA levels resulting in convulsions attenuation.

Topics: Animals; Anticonvulsants; beta-Cyclodextrins; Epilepsy; gamma-Aminobutyric Acid; Nanostructures; Neuropeptide Y; Polymers; Powders; Solubility

Despite the numerous pharmacological activities of quercetin, its biomedical application has been hampered, because of poor water solubility and low oral bioavailability. In the present study, we fabricated a novel form of quercetin-conjugated Fe. Quercetin-loaded NPs were prepared using an iron oxide core coated with βCD and pluronic F68 polymer. The chronic model of epilepsy was developed by intraperitoneal injection of pentylenetetrazole (PTZ) at dose of 36.5 mg/kg every second day. Quercetin or its nanoformulation at doses of 25 or 50 mg/kg were administered intraperitoneally 10 days before PTZ injections and their applications continued 1 hour before each PTZ injection. Immunostaining was performed to evaluate the neuronal density and astrocyte activation of hippocampi.. Our data showed successful fabrication of quercetin onto Fe. Overall, quercetin-Fe

Topics: Animals; Astrocytes; beta-Cyclodextrins; Disease Models, Animal; Epilepsy; Hippocampus; Kindling, Neurologic; Magnetite Nanoparticles; Male; Mice; Neurons; Pentylenetetrazole; Quercetin; Spectroscopy, Fourier Transform Infrared

Intravenous (IV) formulations are useful when treating patients where oral administration is not possible and to study certain pharmacokinetic parameters such as bioavailability. We developed a stable-labeled IV formulation of lamotrigine (LTG) for studying pharmacokinetics in epilepsy patients.. Stable-labeled IV LTG was given to 20 persons with epilepsy (6 men; 14 women) with a mean age of 34.8 years (SD 11.7). A 50mg dose of LTG (stable labeled) was given intravenously and replaced 50mg of the regular morning oral dose of LTG (unlabeled, commercially available formulation).. No significant changes in blood pressure, heart rate, or adverse events including rash were attributed to administration of a 50-mg dose of the intravenous LTG formulation.. Our results show that LTG base that is complexed with 2-hydroxypropyl-β-cyclodextrin and stable-labeled can be given safely as a tracer replacement dose.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; beta-Cyclodextrins; Drug Administration Schedule; Epilepsy; Female; Humans; Lamotrigine; Male; Middle Aged; Triazines; Young Adult

The objective of the present investigation was to study the ability of sulfobutyl ether(7)-β-cyclodextrin to form an inclusion complex with carbamazepine, an anti-epileptic drug with poor water solubility. The formation of the complex was carried out using the industrially feasible spray-drying method. The inclusion complex and physical mixtures were characterized by various techniques such as differential scanning calorimetry (DSC), infrared (IR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and molecular modeling. The DSC, IR, and NMR studies confirmed the formation of an inclusion complex between carbamazepine and sulfobutyl ether(7) β-cyclodextrin whereas XRD studies indicated an amorphous nature of the inclusion complex. Molecular modeling studies disclosed different modes of interaction between carbamazepine and sulfobutyl ether(7) β-cyclodextrin with good correlation with experimental observations. The inclusion complex exhibited significantly higher in vitro dissolution profile as compared with pure carbamazepine powder. The in vivo anti-epileptic activity of carbamazepine/sulfobutyl ether(7) β-cyclodextrin complex was evaluated in pentylenetetrazole-induced convulsions model. The carbamazepine/sulfobutyl ether(7) β-cyclodextrin complex showed significantly higher anti-epileptic activity (p <0.01) as compared with that of carbamazepine suspension on oral administration.

Topics: Administration, Oral; Animals; Anticonvulsants; beta-Cyclodextrins; Calorimetry, Differential Scanning; Carbamazepine; Chemistry, Pharmaceutical; Disease Models, Animal; Drug Carriers; Drug Compounding; Epilepsy; Magnetic Resonance Spectroscopy; Mice; Microscopy, Electron, Scanning; Models, Molecular; Pentylenetetrazole; Solubility; Spectrophotometry, Infrared; Technology, Pharmaceutical; X-Ray Diffraction

To study the effects of Annao tablet (main component is beta-asarone) on S100B and NPY of cortex in chronic epilepsy rats.. The remedy was administered orally. The effects were observed in convulsion model induced by PG, then S100B protein and NPY of cortex were determined.. Annao tablet could depress the epileptic degree, postpone spasm latent period and reduce the wet dog sample (WDS) times. The remedy could decline S100B and NPY of cortex in chronic epilepsy rats.. Annao tablet has obvious antiepileptic effects and can reduce the nerve cell damage induced by epilepsy.

Topics: Acorus; Allylbenzene Derivatives; Animals; Anisoles; Anticonvulsants; beta-Cyclodextrins; Cerebral Cortex; Drug Carriers; Epilepsy; Female; Male; Neuropeptide Y; Plants, Medicinal; Rats; Rats, Sprague-Dawley; S100 Proteins; Tablets

The convulsions of approximately 25% of epileptics are inadequately controlled by currently available medication; therefore the preparation of new antiepileptic drugs is of great interest. Aryl semicarbazones can be considered a new class of compounds presenting anticonvulsant activity. In addition, they can be orally administered and are more active as anticonvulsants than mephenytoin or phenobarbital. However, one disadvantage of these compounds is their low water solubility. As a strategy to circumvent this problem, a 1:1 inclusion compound of benzaldehyde semicarbazone (BS) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was prepared and characterized. The anticonvulsant activities of the free semicarbazone and of the inclusion compound were evaluated in rats using the maximum electroshock and audiogenic seizures screenings. In both tests the minimum dose of compound necessary to produce activity decreases from 100mg/kg for the free semicarbazone to 35 mg/kg for the inclusion compound, indicating a significant increase in the bio-availability of the drug.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Anticonvulsants; Benzaldehydes; beta-Cyclodextrins; Cyclodextrins; Electroshock; Epilepsy; Humans; Magnetic Resonance Spectroscopy; Molecular Structure; Rats; Rats, Wistar; Seizures; Semicarbazones; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction

Topics: Acetates; Aged; AIDS Vaccines; American Medical Association; Amines; Animals; Anticonvulsants; beta-Cyclodextrins; Cells, Cultured; Clinical Trials as Topic; Cochlear Implants; Complementary Therapies; Constriction, Pathologic; Coronary Artery Bypass; Cyclodextrins; Cyclohexanecarboxylic Acids; Depressive Disorder; Drug Therapy, Combination; Epilepsy; Extracorporeal Membrane Oxygenation; Felbamate; Fetus; Gabapentin; gamma-Aminobutyric Acid; Genetic Therapy; Health Care Costs; HIV Infections; Humans; Hyperlipoproteinemia Type II; Lamotrigine; Muscle, Smooth; National Institutes of Health (U.S.); Oxygen; Phenylcarbamates; Propylene Glycols; Respiration, Artificial; Respiratory Distress Syndrome; Triazines; United States; Vascular Surgical Procedures