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 ([ 131 I] iodo-CLZ) and radioiodinated optimized formula ([ 131 I] iodo-CLZ-LbPM) were formulated in an excellent radioiodination yield more than 95%. In vivo biodistribution studies of [ 131 I] 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.
Background: Nausea and vomiting during pregnancy (NVP), is one of the most common complaints of pregnant women. Fetus's gender is one that stimulates these complaints. Aim: This study aimed to assess the relationship between fetal sexand pattern of nausea, vomiting and cholasma among pregnant women. Methods: Descriptive research design. Sample size included 400 pregnant women in their third trimester, that divided into four groups (primi-gravida with female fetus, primi-gravida with male fetus, multi-gravida with female fetus and multi-gravida with male fetus), each group haveone hundred women, The study was conducted at antenatal outpatient clinic, Woman's Health Hospital, Assiut University and Qlta Maternal and Child Health Care center, Assiut, Egypt. Data was collected by using interview questionnaire. Results: This study showed there was relationship between gender of the current pregnancy , pattern, onset, time, frequency, end date of nausea, vomiting and cholasma (p-value 0.001, 0.005, 0.001, 0.002, 0.003 and 0.003 respectively). Conclusion: This study revealed that NVP and cholasma are more likely to occur among female fetus than male. Recommendations: Increase mother's knowledge about the effect of pregnancy hormones related changes on thier health through health education program.
We aimed to study the association of fibroblast growth factor-23 (FGF-23) as a novel cardiovascular risk factor with Doppler pulse wave velocity (PWV) as an arterial stiffness measuring tool in hemodialysis (HD) patients. We conducted a cross-sectional study in which blood samples from 86 HD patients were obtained to estimate FGF 23 and other parameters. Flow waveforms were obtained at two locations within right common carotid artery, and right femoral artery by Doppler ultrasound with ECG recorded in addition. The time differences between the R wave of the ECG signal and the onset of the flow waveforms at the two sites yield ΔT. Distances between sampling sites were measured using a tape measure. PWV was defined as (m/s) = D (m)/ ΔT (s). In the current study, we found significant positive correlations between Doppler PWV and both age (r = 0.401, P = 0.039) and systolic blood pressure (r = 0.602, P = 0.034), while no significant association between Doppler PWV and FGF-23 (r = 0.123, P = 0.259) could be detected. Serum FGF-23 levels are not significantly associated with Doppler PWV in HD patients.
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