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Journal Drug Design, Development and Therapy

2,335 articles
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Drug Design, Development and Therapy; doi:10.2147/dddt

Abstract:An international, peer-reviewed, Open Access journal that spans the spectrum of drug design and development through to clinical applications. The journal is characterized by the rapid reporting of application notes, reviews, original research and clinical studies in all therapeutic areas.
Ahmed Khames
Drug Design, Development and Therapy, Volume 13, pp 925-940; doi:10.2147/dddt.s196425

Abstract:Hexyl alginate derivative, an amphiphilic innovative buccal film-forming material of promising mechanical and release characteristics for the improvement of repaglinide bioavailability
Hong Huang, Houhe Liu, Hua Zhou, Zhiling Liang, Dandan Song, Yun Zhang, Wanqiu Huang, Xiaotian Zhao, Bo Wu, Guodong Ye, et al.
Drug Design, Development and Therapy, Volume 13, pp 881-896; doi:10.2147/DDDT.S180842

Abstract:Sucrose allyl ether (SAE) containing hemostatic drugs and a photoinitiator was established to treat mild postpartum hemorrhage or long-term continuous abnormal uterine bleeding in minimally invasive surgery (MIS) using a photopolymerization method. Real-time infrared spectroscopy and rheological experiments showed that the SAE monomer with shear-thinning characteristics could polymerize rapidly into a transparent membrane. Cytotoxicity experiments in vitro showed that this system could elicit a long-term hemostatic effect. Tissue adhesion was also evaluated. The photo-stability of four delivered antifibrinolytic drugs (6-aminocaproic acid, ethylenediaminediacetic acid, tranexamic acid and p-(aminomethyl) benzoic acid) was tested by ultraviolet-photolysis experiments and illustrated by time-dependent density functional theory. Sustained-release experiments revealed that the formed film could be used as a drug carrier. Molecular docking and molecular dynamics were done to investigate the binding mechanism between hemostatic drugs as ligands and the human plasminogen kringle-1 (1HPK) as a target. It has been suggested that SAE with tranexamic acid could be a drug-release system of microchannel transport used in MIS. This system could tackle the dilemma of fluidity and adhesion in MIS. The photo-stable tranexamic acid was the most suitable drug according to its satisfactory binding energy, good photo-stability, and sustained release.
Xianhui Kang, Xiaodong Tang, Yang Yu, Fangping Bao, Shuyuan Gan, Wei Zheng, Jian Zhang, Shengmei Zhu
Drug Design, Development and Therapy, Volume 13, pp 871-879; doi:10.2147/DDDT.S195221

Abstract:This retrospective cohort study aimed to investigate the association between intraoperative dexmedetomidine infusion and emergence agitation (EA), and recovery profiles after lung surgery in adult patients. It was hypothesized that dexmedetomidine was associated with reduced EA and improved recovery profiles. A single-center chart review was conducted on elective lung surgeries in adults between January and December 2016. The primary outcome was the incidence of EA in postanesthesia care units (PACUs). The secondary outcomes included rescue analgesia, shivering, time to extubation, residual sedation, postoperative pulmonary events, duration of PACU stay, length of hospital stay, and intraoperative hemodynamic changes. Univariate and multivariate regression analyses were used to analyze data. Among 2,468 patients, 814 received an intraoperative dexmedetomidine infusion. Intraoperative dexmedetomidine infusion was associated with a lower incidence of EA (10.9% vs 15.0%; adjusted OR, 0.67; 95% CI, 0.51–0.87; P=0.003), rescue analgesia (7.6% vs 12.2%; adjusted OR, 0.63; 95% CI, 0.47–0.86; P=0.003), shivering (4.2% vs 6.6%; adjusted OR, 0.58; 95% CI, 0.38–0.88; P=0.010), and intraoperative bradycardia (18.6% vs 12.6%; adjusted OR, 1.51; 95% CI, 1.19–1.92; P=0.001). No differences were observed in residual sedation, duration of PACU stay, postoperative pulmonary events, and length of hospital stay between the groups. This retrospective study suggested that intraoperative dexmedetomidine infusion was associated with a lower incidence of EA, rescue analgesia, and shivering in adults after lung surgery. Intraoperative bradycardia was the main side effect.
Tianbiao Zhou, Shujun Lin, Shen Yang, Wenshan Lin
Drug Design, Development and Therapy, Volume 13, pp 857-869; doi:10.2147/DDDT.S189156

Abstract:The purpose of this study was to detect the efficacy and safety of tacrolimus (TAC) in induction therapy of patients with lupus nephritis. Associated studies were extracted from the PubMed and the Cochrane Library on July 10, 2018, and applicable investigations were pooled and analyzed by meta-analysis. Data on complete remission (CR), total remission (TR; complete plus partial remission), proteinuria levels, urine erythrocyte number, albumin, glomerular filtration rate, negative rate of ds-DNA, C3 levels, C4 levels, systemic lupus erythematosus disease activity index (SLE-DAI), etc, were extracted and pooled using RevMan 5.3. In the therapeutic regimen of TAC + glucocorticoids (GC) vs cyclophosphamide (CYC) + GC, the results indicated that the TAC group had high values of CR, TR, albumin, and negative rate of ds-DNA, and low values of proteinuria levels and SLE-DAI when compared with those in CYC group (all P0.05). In the therapeutic regimen comprising TAC + MMF + GC vs CYC + GC, multitarget therapy group showed higher values of CR, TR, urinary protein decline, and rise of serum albumin when compared with CYC group (all P<0.05). TAC is an effective and safe agent in induction therapy of patients with lupus nephritis.
Zhiqing Zhong, Hongyan Li, Hongzhen Zhong, Tianbiao Zhou
Drug Design, Development and Therapy, Volume 13, pp 845-856; doi:10.2147/DDDT.S195113

Abstract:Long-term treatment programs with low toxicity represent a therapeutic challenge in lupus nephritis (LN). Although a therapeutic benefit of rituximab (RTX) has been reported in LN patients who have failed conventional treatment, the results are controversial. We aimed to assess the clinical efficacy and safety of RTX as a new immunosuppressive medicine in the treatment of LN with a meta-analysis. Based on predetermined criteria, PubMed, Embase, and Cochrane Library were used to identify the eligible studies. Cochrane Review Manager version 5.3 was applied to pool the data extracted from individual investigations and provide summary effect estimates. Twenty-four studies with 940 patients were analyzed. In case series trials with specific LN assessment, the complete remission (CR) rate at 12 months was 35.9% (95% CI: 24.2%–49.5%), and total remission (TR: CR plus partial remission) was 73.4% (95% CI: 66.0%–79.7%). In controlled trials, RTX was associated with a higher probability of TR (OR =2.02, 95% CI: 1.23–3.32, P0.05). Additionally, RTX treatment significantly decreased proteinuria (mean difference: −2.79, 95% CI: −3.95 to −1.62, P<0.01) as well as the renal activity index in patients with LN (mean difference: −3.46, 95% CI: −4.43 to −2.50, P<0.01). In controlled trials, the relative risks of the adverse events of infection and infusion reaction were not notably different between the two groups. RTX is a promising therapy for the treatment of LN due to significant clinical efficacy and a favorable safety profile. In future studies, larger study populations and longer-term time points may identify additional important patient-centered outcomes.
Sylwia Flis, Tomasz Chojnacki
Drug Design, Development and Therapy, Volume 13, pp 825-843; doi:10.2147/DDDT.S191303

Abstract:Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells. At the molecular level, the disorder results from t(9;22)(q34;q11) reciprocal translocation between chromosomes, which leads to the formation of an oncogenic BCR–ABL gene fusion. Instead of progress in the understanding of the molecular etiology of CML and the development of novel therapeutic strategies, clinicians still face many challenges in the effective treatment of patients. In this review, we discuss the pathways of diagnosis and treatment of patients, as well as the problems appearing in the course of disease development. We also briefly refer to several aspects regarding the current knowledge on the molecular basis of CML and new potential therapeutic targets.
Marc S. Rendell
Drug Design, Development and Therapy, Volume 13, pp 817-824; doi:10.2147/DDDT.S144556

Abstract:Gene knockout has been a powerful technique to evaluate the physiologic role of selected gene products. Lexicon pioneered high-throughput gene knockout technology and went further in designing agents to inhibit products of gene expression. Two agents have entered late-stage development. Telotristat is an inhibitor of tryptophan hydroxylase (TPH), preventing the production of serotonin. Although this agent blocks the two isoforms of TPH, it does not cross the blood–brain barrier, thus avoiding central neurologic manifestations. It inhibits the peripheral production of serotonin, and in particular prevents serotonin action in the intestines, resulting in decreased peristaltic action. Lexicon successfully developed telotristat to treat carcinoid syndrome not responding adequately to somatostatin inhibitors. Sotagliflozin development proceeded from the observation that dual inhibition of SGLT2 in the kidneys and SGLT1 in the intestines resulted in increased renal glucose excretion, reduced early-phase glucose absorption, as well as increased blood levels of GLP-1 and PYY. Initial development efforts focused on type 1 diabetes and have shown reduced postprandial glucose levels, less tendency to hypoglycemia, and lower HbA1c. Several other SGLT2 inhibitors have been associated with increased frequency of diabetic ketoacidosis (DKA). In the type 1 trials, sotagliflozin-treated individuals experienced DKA at a higher rate than placebo-treated patients. The sotagliflozin development program has now been extended to trials on type 2 diabetes. Long-term clinical trials will determine the benefits and risks of the agent in comparison to other currently marketed SGLT2 inhibitors.
Austin Hoggarth, Andrew Weaver, Qinqin Pu, Ting Huang, Jacob Schettler, Feng Chen, Xiefang Yuan, Min Wu
Drug Design, Development and Therapy, Volume 13, pp 909-924; doi:10.2147/dddt.s189847

Abstract:Mechanistic research holds promise for bacterial vaccines and phage therapies for Pseudomonas aeruginosa Austin Hoggarth,1,* Andrew Weaver,1,* Qinqin Pu,1,* Ting Huang,1,2 Jacob Schettler,1 Feng Chen,3 Xiefang Yuan,3 Min Wu1 1Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA; 2Key Laboratory of Bio-resources and Eco-environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, China; 3Pulmonary and Allergy Institute, Affiliated Hospital of Southwestern Medical University, Luzhou, China *These authors contributed equally to this work Vaccines for Pseudomonas aeruginosa have been of longstanding interest to immunologists, bacteriologists, and clinicians, due to the widespread prevalence of hospital-acquired infection. As P. aeruginosa becomes increasingly antibiotic resistant, there is a dire need for novel treatments and preventive vaccines. Despite intense efforts, there currently remains no vaccine on the market to combat this dangerous pathogen. This article summarizes current and past vaccines under development that target various constituents of P. aeruginosa. Targeting lipopolysaccharides and O-antigens have shown some promise in preventing infection. Recombinant flagella and pili that target TLR5 have been utilized to combat P. aeruginosa by blocking its motility and adhesion. The type 3 secretion system components, such as needle-like structure PcrV or exotoxin PopB, are also potential vaccine targets. Outer membrane proteins including OprF and OprI are newer representatives of vaccine candidates. Live attenuated vaccines are a focal point in this review, and are also considered for novel vaccines. In addition, phage therapy is revived as an effective option for treating refractory infections after failure with antibiotic treatment. Many of the aforementioned vaccines act on a single target, thus lacking a broad range of protection. Recent studies have shown that mixtures of vaccines and combination approaches may significantly augment immunogenicity, thereby increasing their preventive and therapeutic potential. Keywords: lipopolysaccharide, flagella, pili, exoenzymes, outer membrane proteins, phage therapy
Entaz Bahar, Geum-Hwa Lee, Kashi Raj Bhattarai, Hwa-Young Lee, Hyun-Kyoung Kim, Mallikarjun Handigund, Min-Kyung Choi, Sun-Young Han, Han-Jung Chae, Hyonok Yoon
Drug Design, Development and Therapy, Volume 13, pp 907-908; doi:10.2147/dddt.s207534

Abstract:Protective role of quercetin against manganese-induced injury in the liver, kidney, and lung; and hematological parameters in acute and subchronic rat models [Retraction] Bahar E, Lee G-H, Bhattarai KR, et al. Drug Des Dev Ther. 2017;11:2605–2619.The Editor-in-Chief and Publisher of Drug Design, Development and Therapy wish to retract the published article. Concerns were raised about the possibility of image duplication in the published article. Following a review, it was determined the article contained an unacceptable level of image duplication and the findings and conclusions in the presented study were no longer supported. The affected figures within the present article are: ● Figure 5 image Mn, Mn + Qct25 and Mn + Qct50● Figure 6 image Mn, Mn + Qct25 and Mn + Qct50● Figure 9 image Kidney Mn + Qct50 is the samepresented in Figure 10 Kidney Mn + Qct50● Figure 9 Lung Control is the same presented inFigure 9 Lung Mn + Qct25, Mn + Qct50 and Figure10 Lung Control● Figure 9 Lung Mn in the same presented in Figure 10Lung Mn + Qct25● Figure 11 Liver Control is the same presented inFigure 11 Liver Mn + Qct50● Figure 11 Kidney Mn + Qct25 is the same as Figure11 Kidney Mn + Qct50 It was established the author Entaz Bahar acted alone in the image manipulation, however the remaining authors accept accountability for all aspects of the work as part of their publication agreement. Our decision-making was informed by COPE’s retraction guidelines. The authors cooperated throughout the process and agree with the decision to retract. The authors wish to apologize for this error. This retraction relates to this paper
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