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Therapeutic delivery of siRNA for the management of breast cancer and triple-negative breast cancer. 将 siRNA 用于治疗乳腺癌和三阴性乳腺癌。
IF 3 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2024-09-25 DOI: 10.1080/20415990.2024.2400044
Boya Manasa Sai, Yirivinti Hayagreeva Dinakar, Hitesh Kumar, Rupshee Jain, Sharyu Kesharwani, Siddharth S Kesharwani, Shyam Lal Mudavath, Ajmeer Ramkishan, Vikas Jain

Breast cancer is the leading cause of cancer-related deaths among women globally. The difficulties with anticancer medications, such as ineffective targeting, larger doses, toxicity to healthy cells and side effects, have prompted attention to alternate approaches to address these difficulties. RNA interference by small interfering RNA (siRNA) is one such tactic. When compared with chemotherapy, siRNA has several advantages, including the ability to quickly modify and suppress the expression of the target gene and display superior efficacy and safety. However, there are known challenges and hurdles that limits their clinical translation. Decomposition by endonucleases, renal clearance, hydrophilicity, negative surface charge, short half-life and off-target effects of naked siRNA are obstacles that hinder the desired biological activity of naked siRNA. Nanoparticulate systems such as polymeric, lipid, lipid-polymeric, metallic, mesoporous silica nanoparticles and several other nanocarriers were used for effective delivery of siRNA and to knock down genes involved in breast cancer and triple-negative breast cancer. The focus of this review is to provide a comprehensive picture of various strategies utilized for delivering siRNA, such as combinatorial delivery, development of modified nanoparticles, smart nanocarriers and nanocarriers that target angiogenesis, cancer stem cells and metastasis of breast cancer.

乳腺癌是全球妇女因癌症死亡的主要原因。抗癌药物存在靶向性不强、剂量较大、对健康细胞有毒性和副作用等问题,这促使人们关注其他方法来解决这些难题。通过小干扰 RNA(siRNA)进行 RNA 干扰就是其中一种方法。与化疗相比,siRNA 具有多种优势,包括能够快速改变和抑制靶基因的表达,并显示出卓越的疗效和安全性。然而,已知的挑战和障碍限制了其临床转化。裸 siRNA 被内切酶分解、肾脏清除、亲水性、表面负电荷、半衰期短以及脱靶效应等都是阻碍裸 siRNA 发挥预期生物活性的障碍。纳米颗粒系统,如聚合物、脂质、脂聚合、金属、介孔二氧化硅纳米颗粒和其他一些纳米载体,被用于有效递送 siRNA 并敲除乳腺癌和三阴性乳腺癌的相关基因。本综述的重点是全面介绍用于递送 siRNA 的各种策略,如组合递送、开发改性纳米颗粒、智能纳米载体以及针对乳腺癌血管生成、癌症干细胞和转移的纳米载体。
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引用次数: 0
Antimicrobial peptide-fibrin glue mixture for treatment of methicillin-resistant Staphylococcus aureus-infected wounds. 用于治疗耐甲氧西林金黄色葡萄球菌感染伤口的抗菌肽-纤维蛋白胶混合物。
IF 3 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2024-07-16 DOI: 10.1080/20415990.2024.2369497
Mehran Bahreini, Mehrdad Moosazadeh Moghaddam, Masoud Ghorbani, Mohammad Reza Nourani, Reza Mirnejad

Aim: This study was conducted to investigate the effect of fibrin glue-CM11 antibacterial peptide mixture (FG-P) on the healing of infected wounds in vivo.Materials & methods: We formulated a mixture of FG-P and evaluated its antimicrobial activity in vitro against multidrug-resistant (MDR) bacteria involved in wound infection as well as its healing effect on wound infected by methicillin-resistant S. aureus (MRSA) in vivo.Results: The peptide had an MIC of 8 μg/ml against all bacteria isolates. Growth inhibition zones were evident for FG-P compared with FG. The in vivo study showed that the FG-P could be significantly effective in healing the MRSA-infected wound.Conclusion: The use of FG-P mixture is a very suitable option for treating infected wounds.

目的:本研究旨在探讨纤维蛋白胶-CM11 抗菌肽混合物(FG-P)对体内感染伤口愈合的影响。材料与方法:我们配制了一种 FG-P 混合物,并在体外评估了它对伤口感染中的多重耐药(MDR)细菌的抗菌活性,以及在体内评估了它对耐甲氧西林金黄色葡萄球菌(MRSA)感染伤口的愈合效果。研究结果该肽对所有细菌分离物的 MIC 均为 8 μg/ml。与 FG 相比,FG-P 的生长抑制区明显。体内研究表明,FG-P 对愈合 MRSA 感染的伤口有显著效果。结论使用 FG-P 混合物治疗受感染的伤口是一种非常合适的选择。
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引用次数: 0
Application of sphingolipid-based nanocarriers in drug delivery: an overview. 鞘脂类纳米载体在给药中的应用:综述。
IF 3 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2024-07-29 DOI: 10.1080/20415990.2024.2377066
Samarth Kumar, Ajit Singh, Prachi Pandey, Ajay Khopade, Krutika K Sawant

Sphingolipids (SL) are well recognized for their cell signaling through extracellular and intracellular pathways. Based on chemistry different types of SL are biosynthesized in mammalian cells and have specific function in cellular activity. SL has an ampiphilic structure with have hydrophobic body attached to the polar head enables their use as a drug delivery agent in the form of nanocarriers. SL-based liposomes can improve the solubility of lipophilic drugs through host and drug complexes and are more stable than conventional liposomal formulations. Preclinical studies of SL nanocarriers are reported on topical delivery, oral delivery, ocular delivery, chemotherapeutic delivery, cardiovascular delivery and Alzheimer's disease. The commercial challenges and patents related to SL nanoformulations are highlighted in this article.

鞘磷脂(SL)是公认的通过细胞外和细胞内途径传递细胞信号的物质。根据化学原理,哺乳动物细胞中可生物合成不同类型的鞘磷脂,它们在细胞活动中具有特定的功能。脂质体具有双亲结构,疏水体与极性头相连,因此可用作纳米载体形式的药物输送剂。基于 SL 的脂质体可通过宿主与药物的复合物提高亲脂性药物的溶解度,而且比传统的脂质体制剂更稳定。有关 SL 纳米载体的临床前研究报告涉及局部给药、口服给药、眼部给药、化疗给药、心血管给药和老年痴呆症。本文重点介绍了与 SL 纳米制剂有关的商业挑战和专利。
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引用次数: 0
Role of EYP-1901 in neovascular age-related macular degeneration and diabetic eye diseases: review of Phase I/II trials. EYP-1901 在新生血管性老年黄斑变性和糖尿病眼病中的作用:I/II 期试验回顾。
IF 3 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2024-10-03 DOI: 10.1080/20415990.2024.2406226
Abrahem Sayed, Pranesh Ravichandran, Cecilia Canizela, Rehan M Hussain

EYP-1901 (Duravyu) has demonstrated promising outcomes in Phases I and II clinical trials for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME)/diabetic retinopathy. This innovative treatment capitalizes on the potent anti-angiogenic properties of vorolanib, an inhibitor that targets all isoforms of VEGF, effectively mitigating the pathological neovascularization and vascular permeability that underpin these retinal conditions. EYP-1901 is integrated with the Durasert drug delivery system to administer a sustained release of vorolanib directly to the posterior segment of the eye. This delivery system ensures a consistent therapeutic effect over an extended period and significantly reduces the frequency of clinical interventions required, offering a more convenient treatment regimen while maintaining patient safety.

EYP-1901(Duravyu)在治疗新生血管性老年性黄斑变性(nAMD)和糖尿病性黄斑水肿(DME)/糖尿病视网膜病变的 I 期和 II 期临床试验中取得了良好的疗效。Vorolanib 是一种针对血管内皮生长因子所有异构体的抑制剂,这种创新疗法利用了 Vorolanib 的强效抗血管生成特性,有效缓解了支撑这些视网膜病变的病理性新生血管和血管通透性。EYP-1901 与 Durasert 给药系统集成,可直接向眼球后段持续释放沃罗来尼。这种给药系统可确保长期持续的治疗效果,并大大减少所需的临床干预频率,在保证患者安全的同时提供更方便的治疗方案。
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引用次数: 0
Quality-by-design-based microemulsion of disulfiram for repurposing in melanoma and breast cancer therapy. 基于质量设计的双硫仑微乳剂用于黑色素瘤和乳腺癌治疗的再利用。
IF 3 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2024-07-01 DOI: 10.1080/20415990.2024.2363136
Debadatta Mohapatra, Prakash Ch Senapati, Shantibhusan Senapati, Vivek Pandey, Pawan K Dubey, Sanjay Singh, Alakh N Sahu

Aim: The current study aims to develop and optimize microemulsions (ME) through Quality-by-Design (QbD) approach to improve the aqueous solubility and dissolution of poorly water-soluble drug disulfiram (DSF) for repurposing in melanoma and breast cancer therapy.Materials & methods: The ME was formulated using Cinnamon oil & Tween® 80, statistically optimized using a D-optimal mixture design-based QbD approach to develop the best ME with low vesicular size (Zavg) and polydispersity index (PDI).Results: The DSF-loaded optimized stable ME showed enhanced dissolution, in-vitro cytotoxicity and improved cellular uptake in B16F10 and MCF-7 cell lines compared with their unformulated free DSF.Conclusion: Our investigations suggested the potential of the statistically designed DSF-loaded optimized ME for repurposing melanoma and breast cancer therapy.

目的:本研究旨在通过质量源于设计(QbD)方法开发和优化微乳剂(ME),以改善水溶性差的药物双硫仑(DSF)的水溶性和溶解性,从而重新用于黑色素瘤和乳腺癌的治疗。材料与方法:使用肉桂油和吐温®80配制ME,并采用基于D-最佳混合物设计的QbD方法进行统计优化,以开发出具有低囊泡尺寸(Zavg)和多分散指数(PDI)的最佳ME。结果:与未配制的游离 DSF 相比,负载 DSF 的优化稳定 ME 在 B16F10 和 MCF-7 细胞系中显示出更强的溶解性、体外细胞毒性和细胞摄取能力。结论我们的研究表明,经过统计设计的负载 DSF 的优化 ME 有潜力重新用于黑色素瘤和乳腺癌的治疗。
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引用次数: 0
Solid Self Nano-Emulsifying Drug Delivery System of Dasatinib: Optimization, In-vitro, Ex-vivo and In-vivo assessment. 达沙替尼固体自纳米乳化给药系统:优化、体外、体内和体外评估。
IF 3 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2024-09-17 DOI: 10.1080/20415990.2024.2397330
Mohd Aman Mohd Ateeq, Srushti Mahajan, Brojendra Nath Saren, Mayur Aalhate, Hoshiyar Singh, Essha Chatterjee, Indrani Maji, Ujala Gupta, Anitha Sriram, Santosh Kumar Guru, Pankaj Kumar Singh

Aim: Dasatinib (DST) is an oral tyrosine kinase inhibitor with poor aqueous solubility. To outwit this issue, a solid self-nano emulsifying drug delivery system (S-SNEDDS) of DST was formulated.Methods: I-optimal mixture design was used for optimization of DST-loaded SNEDDS using Linalool, Cremophor RH40 and Transcutol P. S-SNEDDS underwent physicochemical characterization, in-vitro release and ex-vivo permeation, cell-based assays and pharmacokinetic study.Results: DST-S-SNEDDS showed globule size and PDI of 141.53 ± 5.371 nm and 0.282 ± 0.020, respectively. DST-S-SNEDDS revealed significantly lower IC50 (1.825 μg/mL) than free DST (7.298 μg/mL) in MDA-MB-231. In-vivo pharmacokinetic study revealed 1.94-fold increment in AUC0-t for the DST-S-SNEDDS group than free DST.Conclusion: S-SNEDDS could be promising approach for improving bioavailability and efficacy of DST.

目的:达沙替尼(DST)是一种口服酪氨酸激酶抑制剂,水溶性较差。为了解决这一问题,我们配制了一种 DST 固体自纳米乳化给药系统(S-SNEDDS):方法:使用芳樟醇、Cremophor RH40 和 Transcutol P 对负载 DST 的 SNEDDS 进行了 I-optimal 混合物设计,并对 S-SNEDDS 进行了理化表征、体外释放和体内渗透、细胞检测和药代动力学研究:结果:DST-S-SNEDDS 的球形尺寸和 PDI 分别为 141.53 ± 5.371 nm 和 0.282 ± 0.020。在 MDA-MB-231 中,DST-S-SNEDDS 的 IC50(1.825 μg/mL)明显低于游离 DST(7.298 μg/mL)。体内药代动力学研究显示,DST-S-SNEDDS 组的 AUC0-t 比游离 DST 组增加了 1.94 倍:结论:S-SNEDDS 是提高 DST 生物利用度和疗效的有效方法。
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引用次数: 0
Recent patents in polymer-lipid hybrid nanoparticles technology. 聚合物-脂质混合纳米粒子技术的最新专利。
IF 3 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2024-07-09 DOI: 10.1080/20415990.2024.2363646
Jyoti Verma, Niraj Kumar Singh, Kuldeep K Bansal
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引用次数: 0
Industry Update, May 2024. 行业最新情况,2024 年 5 月。
IF 3 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2024-08-08 DOI: 10.1080/20415990.2024.2383162
Elaine Harris
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引用次数: 0
Central composite design augmented quality-by-design-based systematic formulation of erlotinib hydrochloride-loaded chitosan-poly (lactic-co-glycolic acid) nanoparticles. 基于中央复合设计的盐酸厄洛替尼负载壳聚糖-聚(乳酸-共羟基乙酸)纳米粒子的质量改进型系统配方。
IF 3 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2024-05-09 DOI: 10.1080/20415990.2024.2342771
Harsh P Nijhawan, Bala Prabhakar, Khushwant S Yadav

Aim: This study aimed to formulate erlotinib hydrochloride (ERT-HCL)-loaded chitosan (CS) and poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using Quality-by-Design (QbD) to optimize critical quality attributes (CQAs). Materials & methods: Quality target product profile (QTPP) and CQAs were initially established. Based on L8-Taguchi screening and risk assessments, central composite design (CCD) design was used to optimize NPs. Results: ERT-HCL-loaded CS-PLGA NPs had a mean particle diameter, zeta potential and entrapment efficiency of 226.50 ± 1.62 d.nm, 27.66 ± 0.64 mV and 78.93 ± 1.94 %w/w, respectively. The NPs exhibited homogenous spherical morphology and sustained release for 72 h. Conclusion: Using systematic QbD approach, ERT-HCL was encapsulated in CS-PLGA NPs, optimizing CQAs. These findings propel future research for improved NSCLC treatment.

目的:本研究旨在采用质量源于设计(QbD)方法配制盐酸厄洛替尼(ERT-HCL)负载壳聚糖(CS)和聚乳酸-聚乙二醇酸(PLGA)纳米颗粒(NPs),以优化关键质量属性(CQAs)。材料与方法:初步确定了目标产品质量曲线(QTPP)和关键质量属性(CQAs)。在 L8-Taguchi 筛选和风险评估的基础上,采用中心复合设计 (CCD) 优化 NPs。结果负载 ERT-HCL 的 CS-PLGA NPs 的平均粒径、zeta 电位和包埋效率分别为 226.50 ± 1.62 d.nm、27.66 ± 0.64 mV 和 78.93 ± 1.94 %w/w。NPs 呈现出均匀的球形形态,并可持续释放 72 小时:利用系统的 QbD 方法,ERT-HCL 被封装在 CS-PLGA NPs 中,优化了 CQAs。这些发现推动了未来改善 NSCLC 治疗的研究。
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引用次数: 0
Organic solvent-free benznidazole nanosuspension as an approach to a novel pediatric formulation for Chagas disease. 无有机溶剂苯并咪唑纳米悬浮剂作为治疗南美锥虫病的新型儿科制剂的一种方法。
IF 3 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2024-08-05 DOI: 10.1080/20415990.2024.2380244
María Sol Magi, Lucía Lopez-Vidal, Mónica Cristina García, Cinthia Carolina Stempin, Constanza Marin, Belkys Maletto, Santiago Daniel Palma, Juan Pablo Real, Alvaro Federico Jimenez-Kairuz

Aim: Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues.Methods: BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC).Results: BNZ-NS exhibited particle size <500 nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90 days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of Trypanosoma cruzi.Conclusion: BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.

目的:苯并咪唑(BNZ)是一种二类药物,是治疗南美锥虫病的主要药物,但其水溶性较低,给配制和疗效带来了挑战。纳米悬浮剂(NS)有可能解决这些问题。方法:采用简单、无有机溶剂的纳米研磨方法制备 BNZ-NS。对纳米悬浮剂和冻干固态 BNZ 纳米晶体(NC)进行了物理化学表征。结果显示BNZ-NS 的粒度与克鲁斯锥虫的粒度一致。结论:BNZ-NSBNZ-NS 是一种很有前景的替代品,它克服了 BNZ 在优化药物治疗方面的局限性。
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引用次数: 0
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Therapeutic delivery
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