Self-Assembling Lecithin-Based Mixed Polymeric Micelles for Nose to Brain Delivery of Clozapine: In-vivo Assessment of Drug Efficacy via Radiobiological Evaluation.

Purpose: The research objective is to design intranasal brain targeted CLZ loaded lecithin based polymeric micelles (CLZ- LbPM) aiming to improve central systemic CLZ bioavailability. Methods: In our study, intranasal CLZ loaded lecithin based polymeric micelles (CLZ- LbPM) were formulated using soya phosphatidyl choline (SPC) and sodium deoxycholate (SDC) with different CLZ:SPC:SDC ratios via thin film hydration technique aiming to enhance drug solubility, bioavailability and nose to brain targeting efficiency. Optimization of the prepared CLZ-LbPM using Design-Expert® software was achieved showing that M6 which composed of (CLZ:SPC: SDC) in respective ratios of 1:3:10 was selected as the optimized formula. The optimized formula was subjected to further evaluation tests as, Differential Scanning Calorimetry (DSC), TEM, in vitro release profile, ex vivo intranasal permeation and in vivo biodistribution. Results: The optimized formula with the highest desirability exhibiting (0.845), small particle size (12.23±4.76 nm), Zeta potential of (-38 mV), percent entrapment efficiency of > 90% and percent drug loading of 6.47%. Ex vivo permeation test showed flux value of 27 µg/cm².h and the enhancement ratio was about 3 when compared to the drug suspension, without any histological alteration. The radioiodinated clozapine ([131I] iodo-CLZ) and radioiodinated optimized formula ([131I] iodo-CLZ-LbPM) were formulated in an excellent radioiodination yield more than 95%. In vivo biodistribution studies of [131I] iodo-CLZ-LbPM showed higher brain uptake (7.8%± 0.1%ID/g) for intranasal administration with rapid onset of action (at 0.25 h) than the intravenous formula. Its pharmacokinetic behavior showed relative bioavailability, direct transport percentage from nose to brain and drug targeting efficiency of 170.59%, 83.42% and 117% respectively. Conclusion: The intranasal self-assembling lecithin based mixed polymeric micelles could be an encouraging way for CLZ brain targeting.

Relation of Liver Siderosis to Liver Fibrosis in Hemodialysis Patients With Severe Hyperferritinemia Secondary to High Doses of Intravenous Iron Supplementation.

OBJECTIVE: Aggressive iron substitution in hemodialysis (HD) patients leads to iron overload. The association between liver siderosis and fibrosis is still debatable. We studied the association of liver siderosis with liver fibrosis in HD patients. Furthermore, we studied the performance of liver stiffness measurements (LSMs) in identifying advanced liver fibrosis. We investigated the performance of biochemical indicators of iron status in identifying advanced liver fibrosis. METHODS: Fifty-five HD patients (average HD duration 6 ± 2 years) with hyperferritinemia secondary to intravenous iron supplementation (weakly iron dose 252.7 ± 63 mg; median blood transfusions 3 [2-5]) were recruited. The liver fibrosis grade was determined with Fibroscan, aminotransferase-to-platelet ratio index (APRI), and Fib-4 index. Liver iron concentration (LIC) was estimated with magnetic resonance imaging (MRI). Iron parameters and liver function biochemical indicators were also assessed. RESULTS: The median serum ferritin and transferrin saturation (TSAT) were 3531 µg/L and 77%, respectively. 34.5%, 20%, and 45.5% of the patients showed mild, moderate, or severe liver siderosis, respectively. All patients with severe liver siderosis showed advanced liver fibrosis. Patients with severe liver siderosis and advanced liver stiffness showed higher serum iron, TSAT, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum bilirubin, APRI, and Fib-4 index scores than those with mild liver siderosis. Serum iron and TSAT showed good utility in identifying advanced liver fibrosis determined with Fibroscan, APRI, and Fib-4 index. Liver stiffness exhibited good utility in identifying advanced liver fibrosis diagnosed with APRI and Fib-4 index. CONCLUSIONS: High weekly intravenous iron dose associated with severe hyperferritinemia, high serum iron, and TSAT might lead to severe liver siderosis and concomitant liver fibrosis in HD patients. Serum iron, TSAT, Fibroscan, Fib-4, and APRI scores might offer noninvasive tools for identifying advanced liver fibrosis in those patients.

Effect of Infant Massage on Salivary Oxytocin Level of Mothers and Infants with Normal and Disordered Bonding.

Maternal-infant bonding is an affective maternal-driven process that occurs primarily to her infant. Prophylactic interventions or treatment of disordered bonding include infant massage. Evidence suggests that oxytocin plays an important role in facilitation of mother-infant bonding. Main objective is to assess the effect of infant massage on salivary oxytocin level of mothers and their infant during postpartum period. And to assess the difference of oxytocin level in normal and disordered maternal-infant bonding. This study is a quasi-experimental study, carried out on 37 pairs of mothers and their infants from second to sixth month postpartum, attending Basateen Gharb primary health care center (PHC) in Albasateen district, Cairo, Egypt. Postpartum Bonding Questionnaire (PBQ) was used to differentiate between mothers with normal and disordered bonding. Pre and post massage salivary samples were taken from mothers and their infants. Tappan's technique of infant massage was used. Results showed that 48.6% (N = 18) of mothers had disordered maternal infant bonding. Mothers and infants with normal bonding showed a positive relationship with their salivary oxytocin level post massage. On the other hand, mothers and infants with disordered bonding showed no change in their salivary oxytocin level post massage. Salivary oxytocin level in male infants has decreased post massage, while oxytocin level in female infants has increased post massage in mothers with normal bonding. We concluded that infant massage increases salivary oxytocin level in mothers and infants with normal bonding and it has no effect on salivary oxytocin level of mothers and infants with disordered bonding.

Effectiveness of Coelatura aegyptiaca Extract Combination with Atorvastatin on Experimentally Induced Hyperlipidemia in Rats.

BACKGROUND: The present study aimed to assess the effectiveness of clam extract in combination with atorvastatin against experimentally hyperlipidemia in rats. METHOD: Forty male rats were divided into 5 groups (8 rats /group): control, high fat diet (HFD), atorvastatin (AROR), clam extract (CE), and ATOR + CE. RESULTS: The treatments with ATOR and /or CE significantly reduced the body weight gain, AST, ALT, ALP, TL, TC, TG, LDL-C, urea, creatinine, and uric acid levels while they increased total proteins, albumin, and HDL-C. The treatment with ATOR only did not cause any significant change in CK and MDA along with antioxidant system, while the treatment with CE alone or with ATOR significantly decreased CK and MDA accompanied by improving the antioxidant system. CONCLUSION: Combination of CE extract with atorvastatin improved the hyperlipidemic efficacy and reduced undesirable side effects especially on muscle.