Oral Delivery of Psoralidin by Mucoadhesive Surface-Modified Bilosomes Showed Boosted Apoptotic and Necrotic Effects against Breast and Lung Cancer Cells

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).This study aims to design and optimize chitosan-coated bilosomal formulations loaded with psoralidin (Ps-CS/BLs) with improved physicochemical properties, oral bioavailability, and boosted apoptotic and necrotic effects. In this regard, uncoated bilosomes loaded with Ps (Ps/BLs) were nanoformulated using the thin-film hydration technique using different molar ratios of phosphatidylcholine (PC), cholesterol (Ch), Span 60 (S60), and sodium deoxycholate (SDC) (1:0.4:0.2:0.125, 1:0.4:0.2:0.25, and 1:0.4:0.2:0.5, respectively). The best-optimized formulation with respect to size, PDI, zeta potential, and EE% was selected and then coated with chitosan at two different concentrations (0.125 and 0.25 w/v%), forming Ps-CS/BLs. The optimized Ps/BLs and Ps-CS/BLs showed a spherical shape and relatively homogenous size with negligible apparent agglomerations. Additionally, it was demonstrated that coating Ps/BLs with chitosan has significantly increased the particle size from 123.16 ± 6.90 in the case of Ps/BLs to 183.90 ± 15.93 nm in the case of Ps-CS/BLs. In addition, Ps-CS/BLs exhibited higher zeta potential (+30.78 ± 1.44 mV) as compared to Ps/BLs (−18.59 ± 2.13 mV). Furthermore, Ps-CS/BL showed enhanced entrapment efficiency (EE%) of 92.15 ± 7.20% as compared to Ps/BLs (68.90 ± 5.95%). Moreover, Ps-CS/BLs exhibited a more sustained release behavior of Ps compared to Ps/BLs over 48 h, and both formulations were best obeying the Higuchi diffusion model. More importantly, Ps-CS/BLs displayed the highest mucoadhesive efficiency% (74.89 ± 3.5%) as compared to Ps/BLs (26.78 ± 2.9%), indicating the ability of the designed nanoformulation to improve oral bioavailability and extend the residence time inside the gastrointestinal tract upon oral administration. Moreover, upon evaluating the apoptotic and necrotic effects of free Ps and Ps-CS/BLs on human breast cancer cell lines (MCF-7) and human lung adenocarcinoma cell lines (A549), there was a dramatic increase in the percentages of the apoptotic and necrotic cell compared to the control and free Ps. Our findings suggest the possible oral use of Ps-CS/BLs in hampering breast and lung cancers.Peer reviewe

Association of Viral Load in SARS-CoV-2 Patients With Age and Gender

Background: The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global public health emergency. Age and sex are two important factors associated with risks and outcomes of various diseases. COVID-19 morbidity also seems to be affected by patient age and sex. It has been found that older age groups have more severe COVID-19 symptoms and higher fatality rates while children tend to have lower prevalence and milder symptoms than adults. Methods: The study reviewed electronic medical records of COVID-19 patients from Madinah city, Saudi Arabia. The study included all cases who tested positive (n = 3,006) between March 20 and May 22, 2020. Data were obtained from the Health Electronic Surveillance Network (HESN) database. Results: Approximately 80% of the study sample were males and half were in the 30-40-year-old age group. The Ct value of the whole sample ranged from 15.08 to 35, with a mean of 27.44 (SD: 5.23; 95% C.I. = 27.25-27.66). The means of Ct values varied between age groups from 27.05 to 27.82. Analysis of the mean differences between age groups using one-way ANOVA indicated no statistically significant difference among the groups (F6,2999 = 1.63; p-value = 0.135). A comparison of mean Ct values of males (n = 2,422) and females (n = 584) revealed that males had a statistically significant higher mean Ct value (27.61 ± 5.20) than females (26.72 ± 5.31). The difference between the means of the two groups was -0.89 (95% C.I. = -1.36 to -0.42; t-test -3.71; df = 3,004; p-value Conclusion: The study found no statistically significant difference in viral loads between age groups. It showed that females had a higher SARS-CoV-2 viral load compared to males. The findings have implications for preventive strategies. Further studies are needed to correlate viral load with clinical symptoms and outcomes

Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration

Aly A Abdelbary,1 Abdulaziz M Al-mahallawi,1 Mohamed E Abdelrahim,2 Ahmed MA Ali3,4 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 2Department of Clinical Pharmacy, 3Department of Pharmaceutics, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt; 4Department of Pharmaceutics, Faculty of Pharmacy, Taif University, Taif, Saudi Arabia Abstract: Carvedilol (CAR) is a potent antihypertensive drug but has poor oral bioavailability (24%). A nanosuspension suitable for pulmonary delivery to enhance bioavailability and bypass first-pass metabolism of CAR could be advantageous. Accordingly, the aim of this work was to prepare CAR nanosuspensions and to use artificial neural networks associated with genetic algorithm to model and optimize the formulations. The optimized nanosuspension was lyophilized to obtain dry powder suitable for inhalation. However, respirable particles must have a diameter of 1–5 µm in order to deposit in the lungs. Hence, mannitol was used during lyophilization for cryoprotection and to act as a coarse carrier for nanoparticles in order to deliver them into their desired destination. The bottom-up technique was adopted for nanosuspension formulation using Pluronic stabilizers (F127, F68, and P123) combined with sodium deoxycholate at 1:1 weight ratio, at three levels with two drug loads and two aqueous to organic phase volume ratios. The drug crystallinity was studied using differential scanning calorimetry and powder X-ray diffractometry. The in vitro emitted doses of CAR were evaluated using a dry powder inhaler sampling apparatus and the aerodynamic characteristics were evaluated using an Andersen MKII cascade impactor. The artificial neural networks results showed that Pluronic F127 was the optimum stabilizer based on the desired particle size, polydispersity index, and zeta potential. Results of differential scanning calorimetry combined with powder X-ray diffractometry showed that CAR crystallinity was observed in the lyophilized nanosuspension. The aerodynamic characteristics of the optimized lyophilized nanosuspension demonstrated significantly higher percentage of total emitted dose (89.70%) and smaller mass median aerodynamic diameter (2.80 µm) compared with coarse drug powder (73.60% and 4.20 µm, respectively). In summary, the above strategy confirmed the applicability of formulating CAR in the form of nanoparticles loaded on a coarse carrier suitable for inhalation delivery. Keywords: aerodynamic diameter, freeze-drying, artificial neural networks, Pluronics, nanosizing, cascade impacto

Occupational infection and needle stick injury among clinical laboratory workers in Al-Madinah city, Saudi Arabia

Abstract Background Clinical laboratory workers face biohazard such as needlestick injury and occupational infection on a daily basis. In this study, we examined self-reported frequency of occupational infection and needlestick injury among the clinical laboratory workers in Al- Madinah, Saudi Arabia. Methods A total of 234 clinical laboratory workers were recruited from private and government health sectors to answer a self-administered questionnaire that was prepared to achieve the aims of the study. Results The results showed that approximately 33% of the sample had an experienced occupational infection while 24% had experienced a needlestick injury. Approximately, 49% reported that they always recap needle after use, whereas 15% reported doing that most of the times. Occupational infection, needlestick injury and recapping needles after use were associated with lack of training on biosafety (P < 0.05). Conclusion The frequency of occupational infection and needlestick injury among clinical laboratory workers in Al-Madinah is high. Interventions related to biosafety and infection control and the use of needlestick prevention devices might be useful in lowering such frequency