Catalina Elena Lupusoru

This paper deals with a comparative study on the interpolymeric complexes of alginate poly(N-isopropyl acryl amide (PNIPAAm) and corresponding graft copolymers with various compositions in respect to their toxicity, biocompatibility and in vitro and in vivo release of theophylline (THP). Loading of the various matrices with theophylline and characterization of loaded matrices was studied by near infrared spectroscopy–chemical imaging (NIR–CI) analysis, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). It was appreciated that THP loading is higher than 40% and the drug is relatively homogeneous distributed within all matrices because of some specific interactions between components of the system. All samples have been found to be non-toxic and biocompatible. It was established that graft copolymers having a good stability show a better drug carrier ability, a higher THP loading, a prolonged release (longer release duration for graft copolymers of 235.4–302.3 min than that for IPC 72/28 of 77.6 min, which means approximately four times slower release from the graft copolymer-based matrices than from the interpolymeric complex) and a good bioavailability. The highest values for THP loading (45%), prolonged release (302.3 min) and bioavailability (175%) were obtained for graft copolymer AgA-g-PNIPAAm 68. The drug release mechanism varies with composition and architecture of the matrix.

Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU)-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI) and sodium form (NaCLI)—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms. The cream (C_BCNU@HCLI) released 29.6% of the loaded BCNU after 12 h in the Nylon synthetic membrane test and 31.6% in the collagen membrane test, higher by comparison to the gel. The new cream was evaluated in vivo in a chemically induced model of skin cancer in mice. Quantitative immunohistochemistry analysis showed stronger inhibition of B-cell lymphoma-2 (bcl-2) and cyclooxygenase 2 (cox-2) protein expression, known markers for cancer survival and aggressiveness, after the treatment with C_BCNU@HCLI by comparison to all the control treatment types, including an off-label magistral formula commercially available Carmustine cream as reference, bringing evidence that a clinoptilolite-based delivery systems could be used as a cancer drug carriers and controlled release systems (skin-targeted topical delivery systems).

Poly(vinyl alcohol)/hyaluronic acid cryogels loaded with methotrexate were studied. The physical–chemical characterization of cryogels was performed by FT-IR spectroscopy, scanning electron microscopy, differential scanning calorimetry and dynamic mechanical thermal analysis. Acute toxicity and haematological parameters were determined by “in vivo” tests. The biocompatibility tests proved that the obtained cryogels showed significantly decreased toxicity and are biocompatible. The pH-responsiveness of the swelling behaviour and of the methotrexate release from the poly(vinyl alcohol)/hyaluronic acid (PVA/HA) cryogels were studied in a pH interval of 2–7.4. A significant change in properties was found at pH 5.5 specific for treatment of affected skin in psoriasis disease.

Zinc chelators were shown to facilitate some opioid-withdrawal signs in animals. Zinc deficiency, which affects more than 15 % the world’s population, is also common among opioid consumers and opioid-treated animals exhibit misbalances of zinc distribution. The present study focuses on how zinc ions interfere with opioid dependence/addiction and analgesia, trying to preliminary discuss if zinc supplementation in opioid-users should be recommended in order to reduce the risk of addiction. All relevant literature was searched up to April 2015. The search was performed using the term “zinc” plus combinations of following terms: “opioid receptors”, “opioid” or representatives of this class, “addiction”, “dependence”, “analgesia”, and “pain”. Human, animal, in vitro studies and reviews were including. Both human and animal studies revealed decreased serum zinc under opioid-administration conditions, attributed mainly to increased urinary elimination (humans) or redistribution (animals). Moreover, animal studies revealed decreased brain zinc levels in morphine-treated animals, with increased zinc hepatic levels, but also an enhancement of endogenous opioid system activity and a possible reduction of morphine withdrawal by zinc. In vitro studies revealed reduction of opioid ligands binding to receptors by zinc. However, the very few in vivo animal studies on opioid analgesia revealed controversial results, as zinc demonstrated clear analgesic effect, but zinc associated to opioids doesn’t result in a potentiation of the analgesic effect. Zinc dietary supplementation in patients treated with opioids for cancer-related chronic pain should be considered, due to the high incidence of zinc deficiency, also well-documented in opioid consumers. The low toxicity of orally-administered zinc also pleads for this idea. The main contra-argument to zinc administration in opioid-treated persons is related to the way zinc influences opioid-induced analgesia.

Discovered in 1984, imidazoline receptors (I1, I2, I3) are located centrally and peripherally being involved in various physiologic and pathophysiologic processes in the body. Experimental and clinical investigations have suggested the interrelations between imidazoline, adrenergic, dopaminergic, glutamatergic and opioid systems, which may explain the influence of different substances acting on imidazoline receptors in cognitive disorders, behavioral disturbances and motor diseases pathways. To investigate the effects of two imidazoline receptor antagonists on locomotor activity and endurance capacity in rats. The experiment was carried out with white male Wistar rats (200-250 g) divided into 3 groups of 7 animals each, treated intraperitonealy with the same volume of solution as follows: Group I (Control): distilled water 0.3 ml/100 g body weight; Group II (IDZ): idazoxan 3 mg/kbw; Group III (EFR): efaroxan 1 mg/kbw. Exercise capacity was evaluated using a locomotor PanLAB treadmill test. The data were presented as mean +/- standard deviation and significance was tested by SPSS Statistics for Windows version 17.0 and ANOVA method. Experimental protocol was implemented according to recommendations of the Gr.T. Popa" University Committee for Research and Ethical Issues. Intraperitoneal administration of idazoxan and efarox- an resulted in a significant increase in running distance compared with the control group (p < 0.05). At the same time a reduction in the number and time of electric shocks delivered to motivate the animal to keep running was observed. In this experimental behavioral model the effects of idazoxan on the evaluated parameters were more intense than those of efaroxan. In our experimental conditions we demonstrated the ability of imidazoline receptor antagonists idazoxan and efaroxan to improve fatigue resistance during forced running in rats.

The study investigates the effects of magnesium nanovesicles on the memory processes performance in mice. L-a-phosphatidylcholine was used to obtain nano formulations as lipid vesicles systems stabilized thereafter with chitosan. The experiment was carried out on white Swiss mice, divided into 3 groups of 7 animals each, treated orally 7 consecutive days: Group I (Control): 0.1 mL/10g distilled water; Group II (Mg): 1 mmol/kbw magnesium chloride; Group III (Mg-vesicles): 1 mmol/kbw magnesium nanovesicles. The spatial memory performance was assessed by recording spontaneous alternation behavior in Y-maze test. Each animal was placed at the end of one arm and allowed to move freely through the maze during a single 8 min session. Alternation was defined as a consecutive entry in three different arms. The alternation percentage was computed according to the formula: (number of alternations/total number of arm visits--2) x 100. Data were analyzed using SPSS 17.0 software. Experimental protocols were implemented according to the recommendations of the University Committee for Research and Ethical Issues. New carrier formulations entrapping magnesium chloride were designed: their mean size was 129.56 nm and the mean Zeta potential was +36.1 mV, indicating a moderate stability of the solution. Oral administration of magnesium vesicles resulted in a significant increase of spontaneous alternation percent in Y-maze test (p < 0.01), which suggests an improvement of short-term memory. Using magnesium chloride entrapped in lipid vesicles induced an enhancement of cognitive functions in mice especially by facilitation of learning extinction.

To investigate the effects of two serotonin receptor antagonists on spontaneous behavior in rats. The experiment was carried out on white male Wistar rats (150-200g) divided into 3 groups of 6 animals each, treated intraperitoneally with the same volume of solution as follows: Group I (Control): saline solution 0.1 ml/10 g weight; Group II (SB-269970): SB-269970 1 mg/kbw; Group III (NAN-190): NAN-190 1 mg/kbw. The effects of serotonin receptor antagonists on the spontaneous psychomotor skills of rats were tested in Actimeter LE-8811 (PanLab). The data were presented as mean +/- standard deviation and significance was tested by SPSS Statistics for Windows version 17.0 and ANOVA method. The experimental protocol was implemented according to the guidelines for handling and use of experimental animals of the Research Ethics Committee of the Iasi "Grigore T. Popa" University and ethical standards of the European Community. The 5HT1 serotonin receptor antagonist NAN-190 determined a statistically significant reduction (p < 0.01) in both horizontal and vertical movements as compared with the control group, whereas the 5HT7 serotonin receptor antagonist SB269970 had no influence on rat behavioral manifestations. In our experimental conditions 1 mg/kbw NAN-190 decreased the total escape attempts, corresponding to a significant diminution of exploratory and self-maintenance spontaneous behavior in this experimental animal model. These manifestations may be correlated with the anxiolytic effect of 5HT1 serotonin receptor antagonist NAN-190 in rats. The administration of 5HT7 serotonin receptor antagonist SB-269970 did not alter the spontaneous activity in this behavioral experimental model in rats.