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Surface-engineered liposomes for dual-drug delivery targeting strategy against methicillin-resistant Staphylococcus aureus(MRSA)

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Asian Journal of Pharmaceutical Sciences 2022年第1期17卷 102-119页

作者： Nur Najihah Izzati Mat Rani Xiang Yi Chen Zahraa M.Al-Zubaidi Hanisah Azhari Tzar Mohd Nizam Khaitir Pei Yuen Ng Fhataheya Buang Geok Chin Tan Yin Ping Wong Mazlina Mohd Said adeel masood butt Azmy A.Hamid Mohd Cairul Iqbal Mohd Amin Centre for Drug Delivery Technology Faculty of PharmacyUniversiti Kebangsaan MalaysiaKuala Lumpur 50300Malaysia Faculty of Pharmacy and Health Sciences University Kuala Lumpur Royal College of Medicine Perak No.3Perak 30450Malaysia Department of Medical Microbiology&Immunology Faculty of MedicineUniversiti Kebangsaan MalaysiaKuala Lumpur 56000Malaysia Drug and Herbal Research Center Faculty of PharmacyUniversiti Kebangsaan MalaysiaKuala Lumpur 50300Malaysia Reading School of Pharmacy University of ReadingReading RG66ADUnited Kingdom Department of Pathology Faculty of MedicineUniversiti Kebangsaan MalaysiaKuala Lumpur 56000Malaysia Institute of Pharmaceutical Sciences University of Veterinary and Animal SciencesLahore 54000Pakistan XORIX Sdn Bhd Dungun Terengganu 23000Malaysia

This study focused on the encapsulation of vancomycin(VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and Nhydroxysuccinimidyl-polyethylene glycol-1,*** formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to confirm the conjugation of the targeting ligand via the formation of amide bonds. Approximately 45% of VAN could be loaded into the aqueous cores, whereas 90% DAPT was detected using UV–vis spectrophotometry. In comparison to free drugs, the formulations controlled the release of drugs for > 72 h. Additionally, as demonstrated using CLSM and flow cytometry, the resulting formulation was capable of evading detection by macrophage cells. In comparison to free drugs, red blood cell membrane–DAPT–VAN liposomes, DAPT liposomes, and VAN liposomes reduced the MIC and significantly increased bacterial permeability, resulting in > 80% bacterial death within 4 h. Cytotoxicity tests were performed in vitro and in vivo on mammalian cells,in addition to hemolytic activity tests in human erythrocytes, wherein drugs loaded into the liposomes and RBCDVL exhibited low toxicity. Thus, the findings of this study provide insight about a dual antibiotic targeting strategy that utilizes liposomes and red blood cell membranes to deliver targeted drugs against MRSA.

关键词： Erythrocyte Dual drug delivery Liposome Methicillin-resistant staphylococcus aureus Vancomycin Daptomycin

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Lipid dysregulation in hepatitis C virus, and impact of statin therapy upon clinical outcomes

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World Journal of Gastroenterology 2015年第27期21卷 8293-8303页

作者： Tracey G Simon adeel A butt Department of Medicine Brigham and Women’s Hospital Harvard Medical School Boston VA Pittsburgh Healthcare System Pittsburgh University of Pittsburgh School of Medicine Hamad Healthcare Quality Institute Hamad Medical Corporation

The hepatitis C virus(HCV) is one of the most common causes of chronic liver disease and the leading indication for liver transplantation worldwide. Every aspect of the HCV life cycle is closely tied to human lipid metabolism. The virus circulates as a lipid-rich particle, utilizing lipoprotein cell receptors to gain entry into the hepatocyte. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation and circulating hypocholesterolemia. Patients with chronic hepatitis C(CHC) are at increased risk of hepatic steatosis, fibrosis, and cardiovascular disease including accelerated atherosclerosis. HMG Co A Reductase inhibitors, or statins, have been shown to play an important role in the modulation of hepatic steatosis and fibrosis, and recent attention has focused upon their potential therapeutic role in CHC. This article reviews the hepatitis C viral life cycle as it impacts host lipoproteins and lipid metabolism. It then describes the pathogenesis of HCV-related hepatic steatosis, hypocholesterolemia and atherosclerosis, and finally describes the promising anti-viral and anti-fibrotic effects of statins, for the treatment of CHC.

关键词： Hepatitis C virus Lipid profiles Cholesterol Statin Fibrosis Cirrhosis

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Phase 3 trial of first generation protease inhibitor therapy for hepatitis C virus/human immunodeficiency virus coinfection

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World Journal of Hepatology 2017年第4期9卷 217-223页

作者： Kenneth E Sherman Minhee Kang Richard Sterling Triin Umbleja Kristen Marks Jennifer J Kiser Beverly Alston-Smith Wayne Greaves adeel A butt 无 Division of Digestive Diseases University of Cincinnati College of Medicine harvard T.h. Chan School of Public health Department of Gastroenterology Virginia Commonwealth University Division of Infectious Disease Weill Cornell Medical School University of Colorado School of Pharmacy NIAID-Division of AIDS Merck and Co Inc. University of Pittsburgh School of Medicine hamad healthcare Quality Institute the ACTG 5294 BIRTH Study Team

AIMTo evaluate efficacy/safety of hepatitis C virus (HCV) protease inhibitor boceprevir with pegylated interferon (PEG-IFN) alfa and weight-based ribavirin (RBV) in a phase 3 trial. METHODSA prospective, multicenter, phase 3, open-label, single-arm study of PEG-IFN alfa, weight-based RBV, and boceprevir, with a PEG-IFN/RBV lead-in phase was performed. The HCV/human immunodeficiency virus coinfected study population included treatment naïve (TN) and treatment experienced (TE) patients. Treatment duration ranged from 28 to 48 wk dependent upon response-guided criteria. All patients had HCV Genotype 1 with a viral load > 10000 IU/mL. Compensated cirrhosis was allowed. Sample size was determined to establish superiority to historical (PEG-IFN plus RBV) rates in sustained viral response (SVR). RESULTSA total of 257 enrolled participants were analyzed (135 TN and 122 TE). In the TN group, 81.5% were male and 54.1% were black. In the TE group, 76.2% were male and 47.5% were white. Overall SVR12 rates (HCV RNA P = 0.002). Among the TN, SVR12 was 42.1% among whites and 27.4% among blacks (P = 0.09). CONCLUSIONThe trial met its hypothesis of improved SVR compared to historical controls but overall SVR rates were low. All-oral HCV treatments will mitigate these difficulties.

关键词： Human immunodeficiency virus Hepatitis C virus Boceprevir Pegylated interferon alfa Ribavirin

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SER estimation method for 56 GBaud PAM-4 transmission system

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Chinese Optics Letters 2018年第4期16卷 30-34页

作者： Aadil Raza Kangping Zhong Salman Ghafoor Saeed Iqbal Muhammad adeel Shahid Habib Muhammad Fasih Uddin butt Chao Lu COMSATS Institute of Information Technology (CIIT) Islamabad Pakistan Department of Electronic and Information Engineering The Hong Kong Polytechnic University Hong Kong China National University of Sciences and Technology (NUST) Islamabad Pakistan

In this Letter, we have proposed a generalized Gaussian probability density function（GGPDF）-based method to estimate the symbol error ratio（SER） for pulse amplitude modulation（PAM-4） in an intensity modulation/direct detection（IM/DD） system. Furthermore, a closed form expression of SERGGDfor PAM-4 has been derived. The performance of the proposed method is evaluated through simulation as well as experimental *** fitting of probability density functions of the received signal is applied via GGPDF and shape parameters P1 and P2 associated with different PAM-4 levels are determined. The optimum single value of shape parameter P is then calculated to estimate the SER. The mathematical relationship of P with different received optical powers and receiver bandwidths has been determined and verified. The proposed method is a fast and accurate method to estimate SER of a PAM-4 system, which is more reliable and in agreement with the error counting method.

关键词： PAM SER estimation method for 56 GBaud PAM-4 transmission system

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Development and Aging Behaviour of Solvent-Based Polychloroprene Rubber Nano-Adhesive Using Multiwall Carbon Nanotubes

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Journal of Materials Science and Chemical Engineering 2020年第9期8卷 31-44页

作者： Muhammad Awais Muhammad Shahid Mohsin Saleem Fariz Aneeq Muhammad Shoaib butt Malik adeel Umer School of Chemical and Materials Engineering National University of Sciences & Technology Islamabad Pakistan

Polychloroprene (PC) based contact adhesives are widely used in various applications;however, there is a possibility to improve the properties of PC adhesive. Modifications of polymers can enhance the properties of the material, e.g. increase in thermal stability, compatibility, rigidity, physical response, flexibility and improve the polymer process ability. In the current study, improved formulation of solvent-based adhesive was developed, and the properties were further enhanced by the addition of nano-reinforcement of multiwall carbon nanotubes (MWCNTs). The addition of nano-reinforcement was optimized to obtain improvement in the bond strength and also to enhance its resistance at a high temperature (~100°C). This paper discusses the uniform dispersion of MWCNTs during the synthesis of polychloroprene solvent-based adhesive, thereby improving its structural properties. Incorporation of MWCNTs-solvent-based adhesives resulted in a 20% - 35% improvement in 180° peel strength determined on flexible substrates such as canvas, leather. The reinforced based adhesive also exhibited improved thermal stability and weather resistance compared with unreinforced adhesive. The MWCNTs- solvent-based contact adhesives is a potential candidate in an industrially relevant branch of adhesives commonly used in structural applications, e.g., footwear, plastic, leather, automobile, construction industries, etc.

关键词： Nanocomposite Polychloroprene Adhesive Peel Strength Carbon Nanotubes

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Digestive system involvement and clinical outcomes among COVID-19 patients:A retrospective cohort study from Qatar

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World Journal of Gastroenterology 2021年第46期27卷 7995-8009页

作者： Muhammad Umair Khan Kamran Mushtaq Deema Hussam Alsoub Phool Iqbal Fateen Ata Hammad Shabir Chaudhry Fatima Iqbal Girisha Balaraju Muna A Al Maslamani Betsy Varughese Rajvir Singh Khalid Al Ejji Saad Al Kaabi Yasser Medhat Kamel adeel Ajwad butt Department of Gastroenterology and Hepatology Hamad Medical CorporationDoha 3050Qatar ECPEExecutive and Continuing Professional Education Harvard T.H Chan School of Public HealthBostonMA 02115-5810United States Department of Palliative Care National Center for Cancer Care&ResearchHamad Medical CorporationDoha 3050Qatar Department of Medicine Hamad Medical CorporationDoha 3050Qatar Department of Infectious Disease Communicable Disease CenterHamad Medical CorporationDoha 3050Qatar Department of Cardiology Research Heart HospitalHamad Medical CorporationDoha 3050Qatar Department of Medicine Division of Infectious DiseasesWeill Cornell Medical CollegeNew YorkNY 10075United States Department of Medicine Weill Cornell Medical College-QatarDoha 24144Qatar

BACKGROUND Coronavirus disease 2019(COVID-19)caused by the severe acute respiratory syndrome coronavirus 2 virus most commonly presents with respiratory *** gastrointestinal(GI)manifestations either at presentation or during hospitalization are also common,their impact on clinical outcomes is *** studies have described worse outcomes in COVID-19 patients with GI symptoms,while others have shown either no association or a protective *** is a need for consistent standards to describe GI symptoms in COVID-19 patients and to assess their effect on clinical outcomes,including mortality and disease *** To investigate the prevalence of GI symptoms in hospitalized COVID-19 patients and their correlation with disease severity and clinical *** We retrospectively reviewed 601 consecutive adult COVID-19 patients requiring hospitalization between May 1-15,*** symptoms were recorded at admission and during ***,clinical,laboratory,and treatment data were *** outcomes included all-cause mortality,disease severity at presentation,need for intensive care unit(ICU)admission,development of acute respiratory distress syndrome,and need for mechanical *** logistic regression model was used to identify independent predictors of the adverse *** The prevalence of any GI symptom at admission was 27.1%and during hospitalization was 19.8%.The most common symptoms were nausea(98 patients),diarrhea(76 patients),vomiting(73 patients),and epigastric pain or discomfort(69 patients).There was no difference in the mortality between the two groups(6.21%vs 5.5%,P=0.7).Patients with GI symptoms were more likely to have severe disease at presentation(33.13%vs 22.5%,P<0.001)and prolonged hospital stay(15 d vs 14 d,P=0.04).There was no difference in other clinical outcomes,including ICU admission,development of acute respiratory distress syndrome,or need for mechanical ventil

关键词： COVID-19 Gastrointestinal manifestations Mortality Intensive care unit admission Mechanical ventilation Disease severity

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