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Synthesis and release studies on amylose-based ester prodrugs of fenamic acid NSAIDs. 基于淀粉糖的非那根酸类非甾体抗炎药酯原药的合成和释放研究。
IF 3 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2024-09-17 DOI: 10.1080/20415990.2024.2400041
Shraddha Chugh, Mousmee Sharma, Garima Chandrasen, Harish Mudila, Parteek Prasher

Aim: To achieve colon-targeted release of mefenamic acid from its ester-linked amylose prodrugs.Materials & methods: The prodrug was characterized by 1H NMR and IR spectroscopy. Drug activation and release profile was studied in enzyme enriched simulated physiological media via UV-vis spectroscopy and was validated with HPLC analysis. ELISA assay was employed for evaluating the % inhibition of COX-1 and COX-2 inhibition at different concentrations of the prodrug preincubated with ester and/ or amylose hydrolyzing enzymes. SEM studies further validated the performance of the prodrug under simulated physiological conditions.Results: Pancreatin was essential for the prodrug activation in SIM to make the ester bonds in prodrug vulnerable to hydrolysis by esterase. This evidence was confirmed by drug release studies, HPLC analysis, ELISA assay and SEM investigation where the ester conjugated prodrug showed marked stability in physiological media only to get activated in the presence of amylose degrading enzyme.Conclusion: Ester linked amylose-mefenamic acid conjugate showed both enzyme responsive activation and release in SIM.

材料与方法:通过酯联淀粉原药实现甲灭酸的结肠靶向释放:通过 1H NMR 和 IR 光谱对原药进行表征。在富含酶的模拟生理介质中,通过紫外可见光谱对药物的活化和释放曲线进行了研究,并通过高效液相色谱分析进行了验证。酶联免疫吸附试验(ELISA)用于评估不同浓度的原药与酯和/或淀粉水解酶预孵育时对 COX-1 和 COX-2 的抑制率。扫描电镜研究进一步验证了原药在模拟生理条件下的性能:结果:胰蛋白酶是 SIM 中原药活化的关键,它使原药中的酯键容易被酯酶水解。这一证据通过药物释放研究、高效液相色谱分析、酶联免疫吸附试验和扫描电镜研究得到了证实,在这些研究中,酯结合原药在生理介质中表现出明显的稳定性,只有在淀粉降解酶存在时才会被激活:结论:酯类连接的淀粉-甲灭酸共轭物在 SIM 中表现出酶反应性激活和释放。
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引用次数: 0
Fabrication of dual drug-loaded polycaprolactone-gelatin composite nanofibers for full thickness diabetic wound healing. 制备用于全厚度糖尿病伤口愈合的双重药物负载聚己内酯-明胶复合纳米纤维。
IF 4.2 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-12-21 DOI: 10.4155/tde-2023-0083
Manjit Manjit, Manish Kumar, Krishan Kumar, Madhukiran R Dhondale, Abhishek Jha, Kanchan Bharti, Zinnu Rain, Pradyot Prakash, Brahmeshwar Mishra

Aim: Design of moxifloxacin and ornidazole co-loaded polycaprolactone and gelatin nanofiber dressing for diabetic wounds. Materials & methods: The composite nanofibers were prepared using electrospinning technique and characterized for in vitro drug release, antibacterial activity, laser doppler and in vivo wound healing. Results: The optimized nanofiber demonstrated an interconnected bead free nanofiber with average diameter <200 nm. The in vitro drug release & antimicrobial studies revealed that optimized nanofiber provided drug release for >120 h, thereby inhibiting growth of Escherichia coli and Stapyhlococcus aureus. An in vivo wound closure study on diabetic rats found that optimized nanofiber group had a significantly higher wound closure rate than marketed formulation. Conclusion: The nanofiber provided prolonged drug release and accelerated wound healing, making it a promising candidate for diabetic wound care.

目的:设计用于糖尿病伤口的莫西沙星和奥硝唑共负载聚己内酯和明胶纳米纤维敷料。材料与方法:采用电纺丝技术制备复合纳米纤维,并对体外药物释放、抗菌活性、激光多普勒和体内伤口愈合进行表征。结果:体外药物释放和抗菌研究表明,优化纳米纤维的药物释放时间超过 120 小时,从而抑制了大肠杆菌和金黄色葡萄球菌的生长。对糖尿病大鼠进行的体内伤口闭合研究发现,优化纳米纤维组的伤口闭合率明显高于市售制剂。结论纳米纤维可延长药物释放时间并加速伤口愈合,因此有望用于糖尿病伤口护理。
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引用次数: 0
Delivering Volume 15: welcome to another year of Therapeutic Delivery! 交付》第 15 卷:欢迎来到《治疗交付》的又一年!
IF 4.2 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-12-20 DOI: 10.4155/tde-2023-0126
Rebecca Turner
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引用次数: 0
A narrative review on Naringin and Naringenin as a possible bioenhancer in various drug-delivery formulations. 关于柚皮苷和柚皮苷在各种给药配方中可能用作生物增效剂的综述。
IF 4.2 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-12-01 Epub Date: 2023-12-13 DOI: 10.4155/tde-2023-0086
Pradeepti Ganesh, Vanishree Suresh, Manoj Kumar Narasimhan, Sarvesh Sabarathinam

Naringenin belongs to the flavanones and is mainly found in fruits (grapefruit and oranges) and vegetables. Naringenin exhibits lipid-lowering and insulin-like characteristics and is used to treat osteoporosis, cancer and cardiovascular disorders. Their incorporation into drug formulations offers several advantages, including enhanced solubility, improved bioavailability and targeted delivery. Naringin-based formulations are beneficial in cancer, for example controlling breast and prostate cancer by inhibition of CYP19. Naringin suppresses the PI3K/AKT signalling pathway, it triggers autophagy, which effectively halts the proliferation of gastric cancer cells. Naringin and naringenin co-administration or pre-administration has enhanced the target drug's potency and produced a synergistic effect. This published study demonstrates the potential applications of Naringin and Naringenin as recognized bio-enhancers.

柚皮苷属于黄烷酮类化合物,主要存在于水果(柚子和橘子)和蔬菜中。柚皮苷具有降血脂和类胰岛素的特性,可用于治疗骨质疏松症、癌症和心血管疾病。将柚皮苷添加到药物制剂中具有多种优势,包括提高溶解度、改善生物利用度和靶向给药。基于柚皮苷的制剂对癌症有益,例如通过抑制 CYP19 来控制乳腺癌和前列腺癌。柚皮苷能抑制 PI3K/AKT 信号通路,引发自噬,从而有效阻止胃癌细胞的增殖。柚皮苷和柚皮甙联合给药或预给药可增强靶向药物的效力,产生协同效应。这项已发表的研究证明了柚皮苷和柚皮甙作为公认的生物增强剂的潜在应用价值。
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引用次数: 0
Nanoparticle-based delivery platforms for the enhanced oral delivery of peptides/proteins. 基于纳米颗粒的递送平台,用于增强多肽/蛋白质的口服递送。
IF 4.2 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-12-01 Epub Date: 2023-12-19 DOI: 10.4155/tde-2023-0048
Sara Salatin, Soheila Montazersaheb, Afsaneh Farjami, Samin Hamidi

Biopharmaceutical products are currently well-established in nearly all branches of medicine and are believed to have great potential for the treatment of a broad spectrum of diseases. Peptide/protein drugs exhibit a predominant class of new biopharmaceuticals coming on the market in recent years. Oral delivery of peptides/proteins as a non-invasive therapeutic technique has become an appealing alternative to the parenteral route. However, the efficient oral delivery of peptides/proteins is limited because of their high molecular weight, poor stability and low biodistribution. Nanoparticles (NPs) have shown excellent results in peptide/protein delivery research. In this paper, the use of NPs as delivery systems for peptides/proteins and their ability to be efficiently delivered via the oral route have been described.

目前,生物制药产品在几乎所有医学领域都得到了广泛应用,并被认为在治疗各种疾病方面具有巨大潜力。肽/蛋白质药物是近年来上市的新型生物制药的主要类别。多肽/蛋白质口服给药作为一种非侵入性治疗技术,已成为肠外给药途径的一种有吸引力的替代方法。然而,由于多肽/蛋白质分子量高、稳定性差、生物分布低,其高效口服给药受到了限制。纳米颗粒(NPs)在多肽/蛋白质给药研究中取得了卓越的成果。本文介绍了 NPs 作为肽/蛋白质给药系统的用途及其通过口服途径高效给药的能力。
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引用次数: 0
Quality by design-assisted development of D-α-tocopherol polyethylene glycol 1000 succinate-incorporated gefitinib-loaded cationic liposome(s). 通过设计辅助开发D-α-生育酚聚乙二醇1000琥珀酸-吉非替尼负载阳离子脂质体的质量。
IF 4.2 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-12-01 Epub Date: 2023-11-29 DOI: 10.4155/tde-2023-0075
Lopamudra Mishra, Shuvadip Bhowmik, Rajveer Singh, Preeti Patel, Ghanshyam Das Gupta, Balak Das Kurmi

Aim: Gefitinib-loaded D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes (GEF-TPGS-LIPO+) were developed and optimized by the quality by design (QbD) approach for its potential anticancer effect. Methods/materials: Box-Behnken design (BBD) a systematic design of experiments was added to screen and optimize the formulation variables. Results: GEF-TPGS-LIPO+ shows vesicle size (210 ± 4.82 nm), polydispersity index (0.271 ± 0.002), zeta potential (22.2 ± 0.84 mV) and entrapment efficiency (82.3 ± 1.95). MTT result shows the enhanced cytotoxicity and higher intracellular drug uptake with highest and lowest levels of the reactive oxygen species and NF-κB expressions on A549 lung cancer cells, determined by fluorescence-activated cell sorting flow cytometry. Conclusion: Potential anticancer effect on A549 cells might be found due to cationic liposomal interaction with cancer cells.

目的:研制吉非替尼负载D-α-生育酚聚乙二醇1000琥珀酸酯(TPGS)包被阳离子脂质体(GEF-TPGS-LIPO+),并采用质量设计(QbD)方法对其潜在的抗癌作用进行优化。方法/材料:采用Box-Behnken设计(BBD),采用系统的实验设计对配方变量进行筛选和优化。结果:GEF-TPGS-LIPO+的囊泡大小为210±4.82 nm,多分散性指数为0.271±0.002,zeta电位为22.2±0.84 mV,包封效率为82.3±1.95。MTT结果显示,A549肺癌细胞的细胞毒性增强,细胞内药物摄取增加,活性氧和NF-κB的表达水平最高和最低。结论:阳离子脂质体可能与癌细胞相互作用,对A549细胞具有潜在的抗癌作用。
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引用次数: 0
Engineered exosomes: a promising vehicle in cancer therapy. 工程外泌体:一种前景广阔的癌症治疗工具。
IF 4.2 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-12-01 Epub Date: 2023-12-20 DOI: 10.4155/tde-2023-0131
Farkhondeh Pooresmaeil, Sahar Andi, Behnam Hasannejad-Asl, Shahla Takamoli, Azam Bolhassani

During the past few decades, researchers have attempted to discover an effective treatment for cancer. Exosomes are natural nanovesicles released by various cells and play a role in communication between cells. While natural exosomes have high clinical potential, their inherent limitations have prompted researchers to design exosomes with improved therapeutic properties. To achieve this purpose, researchers have undertaken exosome engineering to modify the surface properties or internal composition of exosomes. After these modifications, engineered exosomes can be used as carriers for delivery of chemotherapeutic agents, targeted drug delivery or development of cancer vaccines. The present study provides an overview of exosomes, including their biogenesis, biological functions, isolation techniques, engineering methods, and potential applications in cancer therapy.

在过去的几十年里,研究人员一直试图找到一种有效的癌症治疗方法。外泌体是由各种细胞释放的天然纳米颗粒,在细胞之间的交流中发挥着作用。虽然天然外泌体具有很高的临床潜力,但其固有的局限性促使研究人员设计出具有更好治疗特性的外泌体。为此,研究人员开展了外泌体工程研究,以改变外泌体的表面特性或内部组成。经过这些改造后,工程外泌体可用作载体,用于递送化疗药物、靶向药物递送或开发癌症疫苗。本研究概述了外泌体,包括其生物发生、生物功能、分离技术、工程方法以及在癌症治疗中的潜在应用。
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引用次数: 0
On the role of nanocarriers in oral drug delivery. 纳米载体在口服给药中的作用。
IF 4.2 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-12-01 Epub Date: 2023-12-13 DOI: 10.4155/tde-2023-0117
Qin Yu, Wei Wu
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引用次数: 0
Anthocyanin-enriched extract from Ribes nigrum inhibits triglyceride and cholesterol accumulation in adipocytes. 富含花青素的黑肋提取物抑制甘油三酯和胆固醇在脂肪细胞中的积累。
IF 4.2 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-01 Epub Date: 2023-11-29 DOI: 10.4155/tde-2023-0018
Laura Montaldo, Alicia Gallo, Gabriela Rocha, Cecilia Csernoch, Mauricio De Marzi, Liliana N Guerra

Aim: Obesity is a chronic pathology of epidemic proportions. Mature adipocytes from a 3T3-L1 cell line were used as in vitro obesity model to test different bioactive compounds. We aim to evaluate cassis (Ribes nigrum) extract antioxidant activity and its antiadipogenic effect on mature adipocytes. Results: We produced an extract by using enzyme that combines cellulase and pectinase; we obtained high yield of the bioactive compound anthocyanin. Extract showed high antioxidant capacity. We conducted in vitro assays by adding the extract to adipocytes culture medium. Extract reduced intracellular levels of triglyceride by 62% and cholesterol by 32%. Conclusion: Enzymatic extract's high antioxidant activity was likely attributable to its high concentration of anthocyanin. This extract inhibits lipid accumulation in adipocytes.

目的:肥胖是一种具有流行性的慢性疾病。采用3T3-L1细胞系成熟脂肪细胞作为体外肥胖模型,检测不同生物活性化合物。本研究旨在评价黑醋栗提取物的抗氧化活性及其对成熟脂肪细胞的抗脂作用。结果:采用纤维素酶和果胶酶相结合的酶制得提取物;我们获得了高收率的生物活性化合物花青素。提取物具有较高的抗氧化能力。我们将提取液加入到脂肪细胞培养液中进行体外实验。提取物使细胞内甘油三酯水平降低62%,胆固醇水平降低32%。结论:酶提物具有较高的抗氧化活性可能与酶提物中花青素含量较高有关。这种提取物抑制脂肪细胞中的脂质积累。
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引用次数: 0
September industry news update. 9月行业新闻更新。
IF 4.2 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-01 Epub Date: 2023-12-07 DOI: 10.4155/tde-2023-0120
Fiona McCartney
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引用次数: 0
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Therapeutic delivery
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