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Novel electrospun implants of Sunitinib can depress ex-vivo ocular neovascularization 新型舒尼替尼电纺丝植入物可抑制离体眼新生血管
Pub Date : 2022-07-15 DOI: 10.5920/bjpharm.1174
Deepakkumar Mishra, Hákon Hrafn Sigurðsson, A. P. Serro, G. Kalesnykas, R. Donnelly, R. Thakur
Choroidal neovascularization (CNV) is one of the hallmark symptoms of Wet Age-related Macular Degeneration (wAMD) and DiabeticRetinopathy(DR) which involves formation of neoangiogenic i.e. formation of new abnormal blood vessels emerging from the choroidal blood vessels and protruding through the retinal layer. The current management of wAMD involves intravitreal injections of anti-VEGF such as ranibizumab and aflibercept. We hypothesized the delivery of small molecule anti-angiogenesis agents such as the Sunitinib by episcleral route could be an effective and less challenging solution for the management of choroidal neovascularization. In this research, we have fabricated the sunitinib-loaded implants that are able of sustained the release of drug and possess improved ocular pharmacokinetics with a non-invasive administration. The novel episcleral implants were fabricated by electrospinning and were tested for different physiochemical and well as in-vitro pharmacokinetic properties. Further, these implants were tested for in-vitro biocompatibility and ex-vivo efficacy for the estimation of pharmacodynamic properties.
脉络膜新生血管(CNV)是湿性年龄相关性黄斑变性(wAMD)和糖尿病视网膜病变(DR)的标志性症状之一,它涉及新血管生成的形成,即从脉络膜血管中形成新的异常血管并突出视网膜层。目前wAMD的治疗包括玻璃体内注射抗vegf如雷尼单抗和阿非利西普。我们假设,小分子抗血管生成药物,如舒尼替尼,通过膜外途径递送可能是脉络膜新生血管管理的有效和较少挑战的解决方案。在这项研究中,我们制造了舒尼替尼负载的植入物,能够持续释放药物,并且具有改善的眼药代动力学和非侵入性给药。采用静电纺丝法制备了新型外膜植入物,并对其进行了不同的理化和体外药代动力学性能测试。此外,这些植入物进行了体外生物相容性和离体功效测试,以估计药效学特性。
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引用次数: 1
Eradication of E. coli and S. aureus by Ciprofloxacin-loaded hydrogel 环丙沙星水凝胶对大肠杆菌和金黄色葡萄球菌的清除作用
Pub Date : 2022-07-15 DOI: 10.5920/bjpharm.1135
Rania Mohammad Mahafdeh, C. McCoy
Hospital-acquired infection is one of the major risks to patients and an economic burden on the healthcare system, and multidrug resistance is a serious complicating factor in providing effective treatment. Novel drug delivery systems for antimicrobial agents can act as a solution for infection. In this study we demonstrate a biomaterial with antimicrobial properties through incorporation of ciprofloxacin into p(HEMA: MMA) polymer. The main aim is to prevent bacterial adherence on these surfaces, presenting a valuable strategy for nosocomial infection control. The adherence percentage of both S. aureus and E. coli were significantly decreased, and eradication to below limit of detection was demonstrated for 24 hr, contributing to decreasing biofilm formation.  
医院获得性感染是患者面临的主要风险之一,也是卫生保健系统的经济负担,多药耐药是提供有效治疗的一个严重复杂因素。抗微生物药物的新型药物输送系统可以作为感染的解决方案。在这项研究中,我们通过将环丙沙星掺入到p(HEMA: MMA)聚合物中,证明了一种具有抗菌性能的生物材料。主要目的是防止细菌粘附在这些表面,为医院感染控制提供了有价值的策略。金黄色葡萄球菌和大肠杆菌的粘附率均显著降低,且24小时后被清除至检测限以下,导致生物膜形成减少。
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引用次数: 0
Dissolution of theophylline from extended-release tablets under cyclic retrograde peristaltic contractions in the Dynamic Colon Model 动态结肠模型循环逆行蠕动收缩下缓释片中茶碱的溶出
Pub Date : 2022-07-14 DOI: 10.5920/bjpharm.1192
Connor O’Farrell, K. Stamatopoulos, M. Simmons, H. Batchelor
The dynamic colon model isa biorelevant in vitro model of the human proximal colon. In vivo, the largeintestine mixes its contents using peristaltic waves that propagate both forwards(antegrade) and backwards (retrograde). This work studies the dissolutionprofile of theophylline from Uniphyllin Continus 200 mg prolonged releasetablets and the distribution of dissolved theophylline in viscosity-enhancedmedia under the influence of a cyclic retrograde peristaltic contraction. At 16-and 24-hours,  and  theophylline dissolved from the tablet and thefluid inside the mimic intestinal system approached homogeneity.
动态结肠模型是人类近端结肠的生物相关体外模型。在体内,大肠利用向前(顺行)和向后(逆行)传播的蠕动波混合其内容物。本文研究了黄连延释片中茶碱的溶出规律,以及在循环逆行蠕动收缩作用下,溶解茶碱在增粘介质中的分布。在16和24小时,茶碱从片剂中溶解出来,模拟肠道系统内的液体接近均匀。
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引用次数: 0
Population PK modelling as an alternative route to bioequivalence 群体PK模型作为生物等效性的替代途径
Pub Date : 2022-07-14 DOI: 10.5920/bjpharm.1186
Parmesh Gajjar, Jake Dickinson, Harri Dickinson, Linette Ruston, Hitesh B. Mistry, Claire Patterson, P. Dickinson
Demonstratingbioequivalence (BE) is important for the development of lower cost genericproducts, and also for approving post-submission manufacturing changes.However, for many complex parenteral products, BE demonstration can be verychallenging. For example, long-acting injectable products are engineered tohave an extended release over several weeks or months, but this also means thata traditional BE study can take many months or years to perform. Here, we summarisehow population PK modelling, which captures differences in PK profiles due topopulation variation, could be used explore hundreds of virtual formulations,and thus determine a range of products that are bioequivalent after bothmultiple and single dosing. This provides a guide for formulation developmentbut also opens alternative, more streamlined routes to BE assessment. 
证明生物等效性(BE)对于低成本仿制药的开发和批准提交后生产变更非常重要。然而,对于许多复杂的肠外产品,BE演示可能非常具有挑战性。例如,长效注射产品被设计为具有数周或数月的延长释放期,但这也意味着传统的BE研究可能需要数月或数年才能完成。在这里,我们总结了如何利用群体PK模型来研究数百种虚拟配方,从而确定在多次和单次给药后具有生物等效性的一系列产品,该模型捕获了由于群体变化而导致的PK谱差异。这为制定方案提供了指导,但也为BE评估开辟了其他更精简的途径。
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引用次数: 0
Antimicrobial cationic surfactant-loaded hydrogel coatings in preventing medical device-associated infections 抗微生物阳离子表面活性剂负载水凝胶涂层在预防医疗器械相关感染中的应用
Pub Date : 2022-07-14 DOI: 10.5920/bjpharm.1078
Xiao Teng, C. McCoy, Caoimhe Clerkin
Hydrogels described herein were developedas anti-microbial coating materials. Three different hydrogels, p(HEMA), p(85%HEMA-co-15% MMA) and p(85% HEMA-co-15% MAA) were loaded with twocationic surfactant, BAK and DDAB, respectively. DDAB owned better effectivity thanBAK in killing S. aureus and E. coli. Compared to unmodifiedp(HEMA), all drug-loaded samples exhibited significant anti-adherence abilityagainst E. coli, but on surfaces of all DDAB-loaded hydrogels, bacteriawere below limit of detection, so DDAB was more effective than BAK inconferring anti-adherent properties.
本文所述的水凝胶是作为抗菌涂层材料开发的。三种不同的水凝胶,p(HEMA), p(85%HEMA-co-15% MMA)和p(85%HEMA-co-15% MAA)分别负载二元表面活性剂BAK和DDAB。DDAB对金黄色葡萄球菌和大肠杆菌的杀伤效果优于bak。与未修饰的HEMA相比,所有载药样品都表现出对大肠杆菌的显著抗粘附能力,但在所有载DDAB的水凝胶表面,细菌都低于检测极限,因此DDAB比BAK更有效地赋予抗粘附性能。
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引用次数: 0
Characterizing RAPIDTM platelet and leukocyte-rich plasma gels – an autologous, point-of-care medicine for diabetic foot ulcer treatment. 表征RAPIDTM血小板和白细胞丰富的血浆凝胶-一种用于糖尿病足溃疡治疗的自体点护理药物。
Pub Date : 2022-07-13 DOI: 10.5920/bjpharm.1178
A. Olszewska, B. Forbes, S. Pitchford, James Rickard
In 2017/18 wound healing cost the NHS 8.3 billion pounds. There is an urgent need for more effective, accessible, and safe treatments. Platelet-rich plasma (PRP) therapies have been emerging since the early 2000s, currently they are used across various medical fields treating conditions from cosmetic procedures through burn treatments to wound healing. RAPIDTM gel is a product for the treatment of diabetic foot ulcers that is currently in stage 2b of clinical trials. This project aims to better understand the properties of the gel and how these are affected by the manufacturing process. The PRP gels were characterized physiochemically by exploring the gel time, exudate release and growth factor content. These data provide a baseline for future studies exploring how variations in manufacturing conditions affect the gel properties.
2017/18年度,伤口愈合花费了NHS 83亿英镑。迫切需要更有效、更容易获得和更安全的治疗方法。富血小板血浆(PRP)疗法自21世纪初开始出现,目前它们被用于各种医疗领域,治疗从美容手术到烧伤治疗再到伤口愈合。RAPIDTM凝胶是一种治疗糖尿病足溃疡的产品,目前处于2b期临床试验。该项目旨在更好地了解凝胶的特性以及这些特性如何受到制造过程的影响。通过凝胶时间、渗出液释放量和生长因子含量等指标对PRP凝胶进行了理化表征。这些数据为未来研究探索制造条件的变化如何影响凝胶性质提供了基础。
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引用次数: 0
Investigating Buffer Effects on Lysozyme Adsorption to Borosilicate Glass 硼硅酸盐玻璃对溶菌酶吸附的缓冲作用研究
Pub Date : 2022-07-13 DOI: 10.5920/bjpharm.1157
Jack D. Downey, A. Crean, K. Ryan
Proteinadsorption refers to the accumulation and adherence of a protein to the surfaceof a solid, but without surface penetration occurring. Proteins can adsorb to avariety of materials that are used in the manufacture, formulation, and storageof protein medicines. This can have unintended consequences such as loss ofexpensive protein product and aggregate formation. Proteinswith low structural and thermal stability can adsorb to interfaces in higherquantities. This study investigates the role ofbuffer composition, and pH on both the adsorption of lysozyme to borosilicateglass and its thermal stability. Using reverse phase HPLC and dynamic scanningfluorimetry, we quantified the amount of adsorbed protein on the substrate andassessed the thermal stability of lysozyme in the bulk solution. The highest amount of adsorbed lysozyme occurred in the sodiumphosphate and histidine-HCl buffers at pH 7.4. Thermal stability analysisshowed that lysozyme had the lowest melt temperature in these buffers. Theresults indicate that lysozyme adsorption and stability may be mediated by pHand ionic strength. 
蛋白质吸附是指蛋白质在固体表面的积累和粘附,但不发生表面渗透。蛋白质可以吸附在各种用于制造、配方和储存蛋白质药物的材料上。这可能会产生意想不到的后果,如昂贵的蛋白质产物的损失和聚集体的形成。结构稳定性和热稳定性较低的蛋白质可以大量吸附在界面上。本研究考察了缓冲液的组成和pH对溶菌酶在硼硅玻璃上的吸附及其热稳定性的影响。利用反相高效液相色谱法和动态扫描荧光法,我们定量了底物上吸附蛋白质的量,并评估了溶菌酶在散装溶液中的热稳定性。在pH为7.4的磷酸钠和组氨酸-盐酸缓冲液中,溶菌酶的吸附量最高。热稳定性分析表明溶菌酶在这些缓冲液中具有最低的熔体温度。结果表明,溶菌酶的吸附和稳定性可能与磷离子强度有关。
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引用次数: 0
Dual stimuli-responsive hydrogels for colon targeted drug delivery. 双重刺激反应水凝胶用于结肠靶向药物递送。
Pub Date : 2022-07-13 DOI: 10.5920/bjpharm.1134
Mohmmad Imad Rabeh, C. McCoy, M. Wylie
Colon targeted drug deliverysystems are promising for the treatment of local diseases. The colon possessesa diverse microbiome that secretes a number of biomolecules, such as enzymes,that can be exploited for targeted drug delivery. Here, we report the synthesisof 2-hydroxyethyl methacrylate and methacrylic acid  copolymer hydrogels crosslinked with an enzyme-sensitivecrosslinking agent. The swelling and drug release properties of hydrogels were observedin pH 1.2, pH 6.5 and pH 7.4, and in the presence of rat cecal content. Swellingstudies revealed pH responsivity of the hydrogels while the release kinetics ofmetronidazole from hydrogels containing an enzyme-labile crosslinker were fasterin the presence of rat cecal content. The results show that dual responsive hydrogelscould provide a promising platform for colonic drug delivery
结肠靶向药物输送系统有望用于局部疾病的治疗。结肠拥有多种多样的微生物组,这些微生物组分泌许多生物分子,例如酶,可以用于靶向药物递送。在这里,我们报道了用酶敏感交联剂交联的2-羟乙基甲基丙烯酸酯和甲基丙烯酸共聚物水凝胶的合成。观察了水凝胶在pH 1.2、pH 6.5和pH 7.4以及存在大鼠盲肠内容物时的溶胀和药物释放特性。肿胀研究显示水凝胶具有pH响应性,而含有酶不稳定交联剂的水凝胶在存在大鼠盲肠内容物时释放甲硝唑的动力学更快。结果表明,双反应性水凝胶为结肠给药提供了一个很有前景的平台
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引用次数: 0
Formulation Design and Functional Characterisation of a Novel Vaginal Mucosal Drug Delivery System 一种新型阴道粘膜给药系统的配方设计和功能表征
Pub Date : 2022-07-13 DOI: 10.5920/bjpharm.1085
Ahmed Alzainy, J. Boateng
The aim of this research wasthe development, characterisation, and optimisation of composite polymer-basedformulations for vaginal drug delivery using metronidazole (MTz) as a modeldrug to treat bacterial infection in the vagina. Blank (BLK) composite waferscomprising carrageenan (CARR) and sodium alginate (SA) were initiallyformulated and tested. However, due to poor physico-chemical properties,further formulations were developed involving combination of carbopol (CARB)with SA or CARB with CARR, modified with hydroxypropylmethyl cellulose (HPMC)in different weight ratios and plasticised with polyethylene glycol (PEG 200).Drug loaded (DL) wafers were obtained by loading selected optimised compositeCARB-CARR or CARR-SA based gels with 0.75% of MTz prior to freeze-drying.Formulations were characterised using texture analyser (hardness,mucoadhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), swellingcapacity and in vitro drug dissolution study using HPLC.
本研究的目的是开发、表征和优化使用甲硝唑(MTz)作为治疗阴道细菌感染的模型药物的阴道给药复合聚合物配方。由卡拉胶(CARR)和海藻酸钠(SA)组成的空白(BLK)复合晶圆最初被配制并测试。然而,由于其较差的物理化学性能,进一步的配方被开发出来,包括CARB (CARB)与SA或CARB与CARR的组合,用不同重量比的羟丙基甲基纤维素(HPMC)改性,并用聚乙二醇(PEG 200)塑化。载药(DL)晶圆是通过在冷冻干燥前用0.75%的MTz装载选定的优化的carb - carr或CARR-SA基复合凝胶获得的。采用质构分析仪(硬度、黏附)、扫描电镜(SEM)、x射线衍射仪(XRD)、溶胀量和高效液相色谱法(HPLC)对制剂进行表征。
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引用次数: 0
Factors governing the formation of THEDESs: A case study with propionic acid NSAIDs and lidocaine 控制theess形成的因素:丙酸非甾体抗炎药和利多卡因的案例研究
Pub Date : 2022-07-13 DOI: 10.5920/bjpharm.1080
Magdy M. Abdelquader, G. P. Andrews, Shu Li, David S. Jones
Deep eutectic solvents (DES) are products of interaction betweensolid parent compounds resulting in a liquid at room temperature due to significantmelting point depression. Such phenomenon has been employed to improve drugs’ biopharmaceuticalbehavior by including at least one API as DES former to produce a therapeuticDES (THEDES). DES physicochemical characteristics are affected by those of the parentcompounds. Investigating such relation can help in tailoring THEDES formationfor specific outcomes. This was done by comparing THEDES of lidocaine witheither of structurally similar ibuprofen or ketoprofen through thermalanalysis, FTIR and rheological studies to highlight the effect of differentphysicochemical properties on the formed THEDES. Eutectic composition for bothproducts was similar, indicating the important role of supramolecularcomplementarity in eutectic point determination. Glass transition (Tg)of drugs seemed to have direct impact on Tg of the formed THEDESwhere higher Tg ketoprofen produced a higher Tg THEDES. Similarly,higher number of hydrogen bonding sites within ketoprofen structure led to moreviscous and thermally stable product. Moreover, the degree of chargeinvolvement in the interaction network was related to pKa of thedrugs. Such findings can help to construct a structural based approach to selectTHEDES components. 
深共晶溶剂(DES)是固体母体化合物之间相互作用的产物,在室温下由于熔点明显降低而形成液体。这种现象已被用于改善药物的生物制药行为,通过包括至少一种API作为DES前体来产生治疗性DES (THEDES)。DES的理化性质受母体化合物的理化性质影响。研究这种关系有助于为特定结果定制THEDES格式。通过热分析、FTIR和流变学研究,比较利多卡因与结构相似的布洛芬或酮洛芬的THEDES,以突出不同的物理化学性质对形成的THEDES的影响。两种产物的共晶组成相似,表明超分子互补性在共晶点测定中的重要作用。药物的玻璃化转变(Tg)似乎对形成的THEDES的Tg有直接影响,其中高Tg的酮洛芬产生较高的Tg THEDES。同样,酮洛芬结构中氢键位点数量越多,产物粘度越高,热稳定性越好。相互作用网络中的电荷参与程度与药物的pKa有关。这些发现有助于构建一种基于结构的方法来选择thedes组件。
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引用次数: 0
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British Journal of Pharmacy
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