An Approach to Enhance the Solubility of an Atypical Antipsychotic Drug, Aripiprazole: Design, Characterization, and Evaluation of Arabinoxylan-Based Nanoparticles

Mehwish Sikander,1 Ume Ruqia Tulain,1 Nadia Shamshad Malik,2 Arshad Mahmood,3,4 Mohammed S Alqahtani,5 Alia Erum,1 Muhammad Tariq Khan2,6 1Faculty of Pharmacy, University of Sargodha, Sargodha, Pakistan; 2Faculty of Pharmacy, Capital University of Science and Technology, Islamabad, Pakistan; 3Faculty of Pharmacy, Al Ain University, Abu Dhabi Campus, Abu Dhabi, United Arab Emirates; 4AAU Health and Biomedical Research Center (HBRC) Al Ain University, Abu Dhabi, United Arab Emirates; 5Nanobiotechnology Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 6Department of Pharmacy, Quaid-i-Azam University, Islamabad, PakistanCorrespondence: Ume Ruqia Tulain, Faculty of Pharmacy, University of Sargodha, Sargodha, Pakistan, Tel +00923316668588, Email [email protected]: Natural polymers have emerged as versatile and sustainable alternatives to synthetic polymers in pharmaceutical and biomedical applications. This study focuses on the extraction of arabinoxylan (AX) from maize husk and its potential as a promising excipient to enhance the solubility and oral bioavailability of Aripiprazole (APZ), a poorly water-soluble antipsychotic drug, offering a robust strategy for overcoming challenges associated with hydrophobic drugs.Methods: APZ-loaded AX nanoparticles were synthesized using the ionotropic gelation technique. The formulation with the highest encapsulation efficiency designated as FN4 was selected for detailed characterization. Various analytical techniques, including Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), and Differential Scanning Calorimetry (DSC), were employed to assess the morphological, crystalline, and thermal properties of the nanoparticles. In vitro release studies were conducted on both simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8) to evaluate drug dissolution behaviour. The everted sac method was utilized to assess the permeation and transport of APZ from the AX-based nanoparticles.Results: The FN4 formulation exhibited an encapsulation efficiency of 88.9% ± 1.77%, with a particle size of 284.4 nm, a polydispersity index (PDI) of 0.346, and a zeta potential of 20.7 mV. SEM analysis revealed a uniform distribution of polyhedral-shaped nanoparticles. XRD and DSC analyses indicated that APZ was in an amorphous state within the nanoparticles. Drug release was more pronounced at pH 6.8, with the AX nanoparticles showing sustained release. The everted sac method demonstrated enhanced permeation of APZ across intestinal membranes, supporting the potential of AX nanoparticles in improving drug absorption.Discussion: The AX-based nanoparticle formulation significantly improved the solubility, pH-dependent release profile, and sustained release of APZ, offering a promising strategy to enhance the oral bioavailability of poorly soluble drugs. These findings suggest that AX nanoparticles could serve as an effective delivery system for enhancing the therapeutic potential of hydrophobic drugs like APZ.Keywords: arabinoxylan, aripiprazole, nanoparticles, bioavailability, solubilit

Evidence-Based Mental Health Programs in Schools: Barriers and Facilitators of Successful Implementation

Although schools can improve children’s access to mental health services, not all school-based providers are able to successfully deliver evidence-based practices. Indeed, even when school clinicians are trained in evidence-based practices (EBP), the training does not necessarily result in the implementation of those practices. This study explores factors that influence implementation of a particular EBP, Cognitive Behavioral Intervention for Trauma in Schools (CBITS). Semi-structured telephone interviews with 35 site administrators and clinicians from across the United States were conducted 6–18 months after receiving CBITS training to discuss implementation experiences. The implementation experiences of participants differed, but all reported similar barriers to implementation. Sites that successfully overcame such barriers differed from their unsuccessful counterparts by having greater organizational structure for delivering school services, a social network of other clinicians implementing CBITS, and administrative support for implementation. This study suggests that EBP implementation can be facilitated by having the necessary support from school leadership and peers

In silico screening of Hippophae rhamnoides polyphenols targeting the RhoA protein as a potential liver cancer treatment

الملخص: أهداف البحث: نظرا لارتباط اشارات بروتينات ''آر اتش أو جي تي بيز'' المضطربة بسرطانات متعددة، يمكن بحثها كهدف محتمل لعلاجات سرطان الكبد. تعتبر نبتة العليق البحري من النباتات الطبية المهمة الموجودة في جبال قراقرم. ويعتقد باحتوائها على مركبات متعددة الفينول قادرة على تثبيط بروتين ''آر اتش أو – أ''، مما قد يوفر تاثيرات مضادة لسرطان الكبد. طرق البحث: تم تحديد المركبات متعددة الفينول في المستخلص الميثانولي للعليق البحري باستخدام التحليل الكروماتوغرافي السائل عالي الكفاءة ثم فحصها للتحري عن امكانياتها المضادة للسرطان عبر الارساء الجزيئي ومحاكاة الديناميكا الجزيئية ضد بروتين ''آر اتش أو – أ''. تم تحديد قيم الانحراف المتوسط الجذري التربيعي وقيم تقلب الجذر المتوسط المربع لكل مركب مختار، تبعها تحليل خصائص الامتصاص والتوزيع والتمثيل الغذائي والإفراز والسمية. النتائج: وجدت المركبات متعددة الفينول حمض الغاليك وحمض الساليسيليك وحمض الكافيك والكيمفيرول والروتين والكيرستين والكومارين وحمض الفيروليك وحمض السينابيك وحمض النبق وحمض الفانيليك وحمض الكلوروجينيك في المستخلص الميثانولي للعليق البحري. بناء على قاعدة ليبنسكي الخماسية ودرجة فينا وحجم التجويف، تم اختيار خمسة روابط لمزيد من البحث حيث تظهر خصائص ملحوظة. وفقا لذلك، تبين حمض الكافيك كمركب بارز مع خصائص امتصاص وتوزيع وتمثيل غذائي وطرح وسمية جذابة ودرجة ارساء ونتائج محاكاة ديناميكية جزيئية مثالية. الاستنتاجات: نظرا لبقائه سليما وارتباطه ببنية البروتين طوال فترة المحاكاة، مما يدل على تفاعل قوي بين البروتين والرابط ويشير لتاثير تثبيطي محتمل، قد يمتلك حمض الكافيك القدرة العظمى على تثبيط بروتين ''آر اتش أو – أ''. وبالتالي، مطلوب مزيد من البحث لدراسة حمض الكافيك كخيار دوائي محتمل للتطوير الدوائي المستقبلي. Abstract: Objective: Because aberrant Rho GTPase signaling has been associated with multiple cancers, it was investigated as a potential target for liver cancer treatment drugs. The important medicinal plant Hippophae rhamnoides, found in the Karakoram Mountains, is believed to contain polyphenols that inhibit RhoA protein, thus potentially eliciting effects against liver cancer. Methods: Polyphenols were identified in the methanolic extract of H. rhamnoides with HPLC, then screened for their anticancer potential against the RhoA protein through molecular docking and molecular dynamic simulations. The RMSD and RMSF values for each selected compound were determined, and ADMET characteristics were analyzed. Results: The polyphenols gallic acid, salicylic acid, caffeic acid, kaempferol, rutin, quercetin, coumarin, ferulic acid, sinapic acid, HB acid, vanillic acid, and chlorogenic acid were found in the methanolic extract of H. rhamnoides. On the basis of Lipinski's rule of five, the Vina score, and the cavity size, we chose five ligands with favorable features for further research. Caffeic acid was the most promising compound, on the basis of favorable ADMET qualities, and the best docking score and MD simulation results. Conclusion: Caffeic acid remained intact and bound the protein structure throughout the simulation run, thus demonstrating a robust interaction between the protein and ligand, and indicating a possible inhibitory effect. Therefore, this compound might have the greatest ability to inhibit the RhoA protein. Further research is required to examine caffeic acid as a potential medication option for future drug development

Implementation Science in School Mental Health: Key Constructs in a Developing Research Agenda

In this paper, we propose an implementation science research agenda as it applies to school mental health (SMH). First, we provide an overview of important contextual issues to be considered when addressing research questions pertinent to the implementation of mental health interventions in schools. Next, we critically review three core implementation components: (a) professional development and coaching for school professionals regarding evidence-based practices (EBPs); (b) the integrity of EBPs implemented in schools; and (c) EBP sustainment under typical school conditions. We articulate research questions central to the next generation of research in each of these areas as well as methods to address such questions. Our intent in doing so is to contribute to a developing blueprint to guide community-research partnerships as well as funding agencies in their efforts to advance implementation science in SMH