In: Ecotoxicology and environmental safety: EES ; official journal of the International Society of Ecotoxicology and Environmental safety, Band 266, S. 115545
In: Ecotoxicology and environmental safety: EES ; official journal of the International Society of Ecotoxicology and Environmental safety, Band 168, S. 205-211
Akhtar Rasul,1,* Muhammad Imran Khan,2,* Mujeeb Ur Rehman,1,* Ghulam Abbas,1,* Nosheen Aslam,3,* Shabbir Ahmad,4,* Khizar Abbas,5,* Pervaiz Akhtar Shah,6,* Muhammad Iqbal,7,* Ali Mohammad Ahmed Al Subari,6,* Talal Shaheer,8,* Shahid Shah9,* 1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan; 2Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, Pakistan; 3Department of Biochemistry, Government College University, Faisalabad, Pakistan; 4Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau, People's Republic of China; 5Department of Pharmacognosy, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan; 6University College of Pharmacy, University of the Punjab, Lahore, Pakistan; 7Faculty of Pharmacy, Gomal University, Dera Ismail Khan, Pakistan; 8Department of Pharmacognosy, Xian Jiaotong University, Xian, People's Republic of China; 9Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan*All authors contributed equally to this workCorrespondence: Akhtar Rasul Email akhtar.rasul@gcuf.edu.pkBackground: Cyclosporine A (CsA) is an exceptional immunosuppressant used for the treatment of immune disorders. Niosomal vesicles are promising drug carriers that are formed by self-association of nonionic surfactants and cholesterol in an aqueous phase. The objective of the study was to formulate combined nonionic surfactant based vesicles and to evaluate their in vitro characterization, release studies and in vivo studies.Materials and Methods: Five niosomal formulations (F7 to F11) were prepared using the thin film hydration method. The molar ratio of cholesterol and non-ionic surfactant taken was 1:1. In formulation F10, the combination of surfactants Span 20 and Brij 35 was used. The niosomes were characterized by zeta sizer and SEM for particle size analysis, in vitro drug release and stability studies. The pharmacokinetic studies were conducted on healthy albino rabbits.Results: The size of niosome was found in the range of 427.1 nm to 972.3 nm. SEM image of optimized formulations F10 exhibit the spherical nature of niosomal vesicles. DSC thermograms of niosomal formulations exhibited a broadened endothermic peak. The stability study exhibited that all formulations are stable and negligible change of vesicle size and entrapment was observed with time. The percentage drug release was significantly higher as compared to CsA plain dispersion for all niosomal formulations at pH 1.2 and 7.4. The release kinetic behavior showed that all preparations were best described by zero order and can release active ingredient in a sustained manner. The pharmacokinetic data showed the test formulation (F10) possessed greater bioavailability as compared to the reference formulation (CsA aqueous dispersion).Conclusion: The formulation F10 demonstrated a comparatively more delayed rate of release with enhanced dissolution as compared to a single surfactant scheme. The F10 formulation can be a remarkable nanotechnology for prolonged delivery of CsA orally with improved dissolution profile and bioavailability.Keywords: in vitro study, cyclosporine A, niosomes, nonionic surfactants
In: Ecotoxicology and environmental safety: EES ; official journal of the International Society of Ecotoxicology and Environmental safety, Band 173, S. 182-191
Mehreen Bashir,1 Junaid Ahmad,1 Muhammad Asif,2 Salah-Ud-Din Khan,3 Muhammad Irfan,1 Asim Y Ibrahim,4 Sajid Asghar,1 Ikram Ullah Khan,1 Muhammad Shahid Iqbal,5 Abdul Haseeb,6 Syed Haroon Khalid,1 Mohammed AS Abourehab7,8 1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, 38000, Pakistan; 2Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 3Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia; 4Faculty of Pharmacy, Omdurman Islamic University, Omdurman, Sudan; 5Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia; 6Department of Clinical Pharmacy, College of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia; 7Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 8Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, EgyptCorrespondence: Syed Haroon KhalidDepartment of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, 38000, PakistanTel +92-3166752223Email syedharoonkhalid@gcuf.edu.pkPurpose: Rheumatoid arthritis is an autoimmune disorder that directly affects joints. However, other body organs including heart, eyes, skin, blood vessels and lungs may also be affected. The purpose of this study was to design and evaluate a nanoemulgel formulation of diflunisal (DIF) and solubility enhanced diflunisal (DIF-IC) for enhanced topical anti-inflammatory activity.Methodology: Nanoemulsion formulations of both DIF and DIF-IC were prepared and incorporated in three different gelling agents, namely carboxymethylcellulose sodium (CMC-Na), sodium alginate (Na-ALG) and xanthan gum (XG). All the formulations were evaluated in term of particle size, pH, conductivity, viscosity, zeta potential and in vitro drug release. The formulation 2 (NE2) of both DIF and DIF-IC which expressed optimum release and satisfactory physicochemical properties was incorporated with gelling agents to produce final nanoemulgel formulations. The optimized nanoemulgel formulation was subjected to three different in vivo anti-inflammatory models including carrageenan-induced paw edema model, histamine-induced paw edema model and formalin-induced paw edema model.Results: DIF-IC-loaded nanoemulgel formulations yielded significantly enhanced in vitro skin permeation than DIF-loaded nanoemulgel. The nanoemulgel formulation of DIF-IC formulated with XG produced improved in vivo anti-inflammatory activity.Conclusion: It was recommended that DIF-IC-based nanoemulgel formulation prepared with XG could be a better option for effective topical treatment of inflammatory conditions.Keywords: diflunisal, nanoemulsion, pseudoternary phase diagram, in vitro skin permeation, anti-inflammatory activity, improved efficacy
Mukhtiar Ahmad,1,* Mehran Khan,2,* Rizwan Asif,3,* Nuzhat Sial,4,* Usman Abid,5,* Tahira Shamim,6 Zahid Hameed,7 Muhammad Junaid Iqbal,8,* Uroosa Sarfraz,8 Hina Saeed,1,* Zara Asghar,2 Madeeha Akram,2 Qamar Ullah,9 Qurat ul Ain Younas,10 Laraib Rauf,11 Alishba Hadi,1 Sajida Maryam,12 Yasir Hameed,1 Muhammad Rashid Khan,13,* Eman Tariq,14 Saba Saeed15,* 1Department of Biochemistry and Biotechnology, Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Department of Pharmacy, Islamia University of Bahawalpur, Bahawalpur, Pakistan; 3Department of Microbiology, Government College University Faisalabad, Faisalabad, Pakistan; 4Department of Zoology, Islamia University of Bahawalpur, Bahawalpur, Pakistan; 5Department of Pharmaceutics, Bahauddin Zakariya University, Multan, Pakistan; 6University College of Conventional Medicine, Islamia University of Bahawalpur, Bahawalpur, Pakistan; 7Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan; 8Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan; 9Department of Livestock and Dairy Development, Peshawar, Pakistan; 10Department of Zoology, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan; 11Department of Healthcare Management, Riphah International University, Islamabad, Pakistan; 12Arid Agriculture University, Rawalpindi, Pakistan; 13University College of Eastern Medicine, Islamia University of Bahawalpur, Bahawalpur, Pakistan; 14Department of Chemistry, University of Swabi, Swabi, Pakistan; 15Department of Zoology, University of the Punjab, Lahore, Pakistan*These authors contributed equally to this workCorrespondence: Yasir Hameed, Department of Biochemistry and Biotechnology, Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan, Email Yasirhameed2011@gmail.comIntroduction: In light of the increased demand for reliable cancer-associated biomarkers and ANLN oncogenic potential, the present study aimed to investigate ANLN's role in 24 human cancers.Methods: The UALCAN, Kaplan–Meier (KM) plotter, TNM Plot, GENT2, GEPIA, HPA, cBioPortal, STRING, Enrichr, TIMER, Cytoscape, DAVID, MuTarget, and CTD online databases and bioinformatic tools were used in this study.Results: In three of the cancers analyzed, ANLN expression was downregulated in tumor tissue, while it was overexpressed in the 21 other types of tumor tissue relative to controls. In CESC, ESCA, HNSC, and KIRC patients, ANLN overexpression was correlated with shorter overall survival, relapse-free survival, and metastasis. This suggests that ANLN is significantly involved in the development and progression of these four cancers. Further expression analysis revealed upregulation of ANLN in CESC, ESCA, HNSC, and KIRC patients with different clinical characteristics, regardless of the heterogeneity barrier. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that ANLN-associated genes were coexpressed with ANLN and were included in diverse BP, MF, and KEGG terms. Moreover, some interesting correlations were also documented between ANLN expression and its promoter-methylation level, genetic alterations, other mutant genes, and CD8+ T- and CD4+ T-cell infiltration. Moreover, we also identified ANLN-associated transcription factors, miRNAs, and chemotherapeutic drugs.Conclusion: This pan-cancer study revealed the novel diagnostic and prognostic role of ANLN across four cancers, regardless of heterogeneity.Keywords: cancer, ANLN, diagnostic, prognostic, biomarker
ImportanceOne major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders.ObservationsNational Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings.Conclusions and relevanceNeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.