Research in Pharmaceutical Sciences
Volume:9 Issue: 5, Oct 2014

The purpose of the present study was to develop glipizide controlled release nanoparticles using alginate and chitosan thorough ionotropic controlled gelation method. Glipizide is a frequently prescribed second generation sulfonylurea which lowers the blood glucose in type-two diabetics. Quick absorption of the drug from the gastrointestinal tract along with short half- life of elimination makes it a good candidate for controlled release formulations. Alginate-chitosan nanoparticles (ACNP) are convenient controlled delivery systems for glipizide, due to both the release limiting properties of the system, and the bioadhesive nature of the polymers. In the present study, glipizide loaded alginate-chitosan nanoparticles (GlACNP) were prepared, and the particle characteristics including particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), loading percent (LP), and mean release time (MRT), as well as the morphology of the nanoparticles, the drug-excipient compatibility, and the release kinetics along with the drug diffusion mechanism were evaluated. The results suggested that ionotropic controlled gelation method offers the possibility of preparing the nanoparticles in mild conditions in an aqueous environment, and can lead to the preparation of particles with favorable size, controlled release characteristics, and high entrapment efficiency, serving as a convenient delivery system for glipizide. The particle and release characteristics can be efficiently optimized using the Box-Behnken design. Based on the findings of the present study, it is expected that this novel formulation be a superior therapeutic alternative to the currently available glipizide delivery systems.

Glutamate has a key role in pain perception and also development of tolerance and dependence to morphine. It has been reported that clavulanic acid affects glutamatergic transmission via activation of glutamate transporter. Therefore the present study was aimed to evaluate the possible antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models. Male Swiss mice (25-30 g) were used in this study. Acetic acid-induced writhing, formalin test and hot plate method were used to assess the antinociceptive effect of clavulanic acid. Morphine (30 mg/kg, s.c.) was administered to the mice two times a day (8 AM and 4 PM) for 3 days in order to produce tolerance. To develop morphine dependence, morphine sulfate (50, 50 and 75 mg/kg) was injected at 8 and 12 AM and 16 PM respectively and for 3 consecutive days. Naloxone (5 mg/kg, i.p) was used to induce morphine withdrawal syndrome and the number of jumps and presence of ptosis, piloerection, tremor, sniffing and diarrhea were recorded and compared with control group. Clavulanic acid at doses of 10, 20 and 40 mg/kg inhibited abdominal constriction and licking behavior of acetic acid and formalin-induced pain respectively. Clavulanic acid was not able to show any antinociception in hot plate model and could not prevent development of tolerance and dependence to morphine. Clavulanic acid has considerable antinociceptive activity and further studies are needed to clarify its exact mechanism.

In this study, caffeic acid (CA) and its three derivatives including 3-caffeoylquinic acid (3-CQA, neochlorogenic acid), 4-caffeoylquinic acid (4-CQA, cryptochlorogenic acid), and 5-caffeoylquinic acid (5-CQA, chlorogenic acid) were identified in Bupleurum chinense aerial parts using reverse-phase high-performance liquid chromatography (RP-HPLC) with photodiode array (PDA) detector, reference compounds and chemical reactions. Separation was performed on a C18 column using gradient elution with 4% (v/v) aqueous acetic acid and acetonitrile as mobile phase at ambient temperature. In addition, the flavonoid aglycones were characterized and quantified after acid hydrolysis of the plant material. The flavonols profile showed quercetin (0.36 g per 100 g), kaempferol (1.11 g per 100 g) and isorhamnetin (0.16 g per 100 g). Total phenolic and total flavonoid contents ranged from 7.3 to 18.7% and 0.58 to 2.72% in dry plant material, respectively.

Cholecystokinin (CCK), a peptide hormone found in the gut, is the most abundant peptide neurotransmitters in the brain, and its acute effects on the brain activity have been shown. In this study we aimed to evaluate the acute effects of CCK on short-term synaptic plasticity in the dentate gyrus (DG) of the rat hippocampus. Via stereotaxic surgery, the stimulating and the recording electrodes were placed in the perforant pathway and dentate gyrus, respectively and 30 min after intraperitoneal (i.p.) injection of CCK octapeptide sulfated (CCK-8S, 1.6 µg/kg), evoked responses were recorded after delivering of paired-pulse stimulations at 10 to 500 ms inter-stimulus intervals. With respect to the control group that received saline instead of CCK, in baseline responses, slope of field excitatory postsynaptic potential (fEPSP) 5 min and 10 min after injection of CCK-8S (p<0.05) and population spikes (PS)-amplitudes 5 min after injection of CCK-8S (p<0.05) were significantly increased. In paired pulse responses, PS amplitudes were increased in the CCK group, but these enhancements only were significant at inter-stimulus interval 40 ms (p<0.05). However fEPSP slopes were decreased at inter-stimulus intervals 70 ms (p<0.05), 120 ms (p<0.01), 150 ms (p<0.001) and 300 ms (p<0.001). The results showed that CCK-8S has a transient excitatory effects on baseline responses, but it inhibits paired pulse indices in acute. Therefore, in a short period of time, effect of CCK on the function of synapses is time dependent, and it has stimulatory or inhibitory effects at different time periods.

Glibenclamide (GLIB) is a poorly soluble drug with formulation-dependent bioavailability. Therefore, we attempted in this study to improve GLIB dissolution rate by preparing drug solid dispersions by solvent evaporation (SE) and supercritical fluid solvent-antisolvent techniques (SCF-SAS). A D-optimal mixture design was used to investigate the effects of different ratios of HPMCE5 (50-100%), PEG6000 (0-40%), and Poloxamer407 (0-20%) on drug dissolution from different solid dispersion (SD) formulations prepared by SE. The ratios of carriers used in SCF-SAS method were HPMCE5 (fixed at 60%), PEG6000 (20-40%), and Poloxamer407 (0-20%). A constant drug: carrier weight ratio of 1:10 was used in all experiments. The SDs obtained were physically characterized and subjected to the dissolution study. The major GLIB bands in FTIR spectra were indicative of drug integrity. The reduced intensity and the fewer number of peaks observed in X-ray diffractograms (XRD) of GLIB formulations was the indicative of at least partial transformation of crystalline to amorphous GLIB. This change and/or dilution of drug in much higher amounts of carriers present caused disappearance of distinctive endothermic peaks in differential scanning calorimetry thermograms of GLIB formulations. The model generated according to the results of the D-optimal mixture design indicated that GLIB formulations comprising HPMC (50%-60%), PEG (34-40%), and poloxamer (6-10%) had enhanced dissolution performances. As compared to SE method, the SCF-SAS technique produced formulations of higher dissolution performances, likely due to the effects of solution and the supercritical CO2 (SC-CO2) on enhanced plasticization of polymers and thus increased diffusion of the drug into the polymer matrix.

Temporal lobe epilepsy (TLE) is a disorder of the central nervous system in which hippocampus is mostly involved and causes memory impairment. Kindling is a model of inducing epilepsy which is created through pentylenetetrazol (PTZ) administration. This study examines the role of the aqueous extract of Boswellia on the learning and development of brain (formation of dendritic branches and axons) of the PTZ-induced kindled rats. The study is conducted on sixty-four male rats divided into 8 groups. Kindling seizures are induced by three injections of 25 mg/kg of PTZ every 15 min. The aqueous extracts (0, 0.1, 0.5, 1 g/kg, i.p) are administrated to all animals for three consecutive days. Passive avoidance learning of animals is examined using shuttle box apparatus and step-through latency (STL) method. Rats are anesthetized and their brains are fixed by transcardial perfusion method and are analyzed by morphometric methods after applying Golgi and Cresyl violet staining methods. PTZ-induced kindling indicates a significant decrease in the number of pyramidal neurons and dendritic spines in hippocampal region cornu ammonis (CA1). The STL of the kindled rats is significantly reduced compared with control ones. Also, Boswellia extract dramatically increased the number of neuronal processes in CA1 region and improves passive-avoidance learning ability in both control and PTZ-kindled animals in 1 g/kg dose administration of Boswellia extract, especially at high doses can eliminate adverse effects of seizures on cognitive function in hippocampal area CA1 in rats.

Tragopogon buphthalmoides (DC.) Boiss, is widely used as a food additive with some imputed health effects in folk medicine of western Iran. Unfortunately, despite the prevalent medicinal uses of the plant, there are no reports on the toxic effects of T. buphthalmoides aerial parts. The present study evaluated the potential toxicity of dried hydroethanolic extract of the species in wistar rats. Also, we investigated antioxidant activity and total phenolic content (TPC) of the extract. In the acute study, single doses of extract were administered orally, and the rats were then monitored for 14 days. In the subchronic toxicity study, the sample was administered to the rats for 45 days. In the antioxidant capacity assays dried extract showed moderate to weak antioxidant activities. Also, the sample showed relatively notable TPC. The results of acute study indicated that the LD50 of T. buphthalmoides is higher than 2500 mg/kg. Biochemical analysis showed some significant changes including creatinine, glucose and triglyceride levels. Moreover, some significant abnormality of lung, kidney and liver organs was observed. Based on the results of this study, adverse effect level (AEL) of dried hydroethanolic extract of T. buphthalmoides considered to be less than 175 mg/kg/day for the male and female rats.

Recently, several studies have shown that the metal-fluoroquinolone complexes have more antibacterial and cytotoxic effects in comparison with free fluoroquinolones. These results may introduce new drugs for chemotherapy with fewer side effects. In this work a bidentated zinc (II) complex with ofloxacin (OZC) was synthesized and cytotoxicity activities and DNA binding of the resulted complex was studied. The in-vitro anti proliferative and cytotoxic effects of the free ofloxacin (OFL) and OZC against MCF-7, CaCo2 and SKNMC cell lines were tested by using Trypan blue and lactate dehyrogenase (LDH) assay methods. Results revealed that the OZC exhibits better anti proliferative and cytotoxic activities as compared with the OFL. This may be due to the more interaction of OZC with DNA. Therefore, the interaction of OZC with DNA was investigated by using voltammetry, UV-Vis, fluorescence, FT-IR and circular dichroism spectroscopy methods, and the equilibrium binding constant (Kb), binding site size, and thermodynamic parameters were measured. The results revealed that the OZC interacts with DNA via two modes: electrostatic and outside hydrogen binding. The proposed DNA binding modes may support the greater in-vitro cytotoxicity of OZC compared to OFL alone.