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Nanoparticle drug delivery systems in hepatocellular carcinoma: A focus on targeting strategies and therapeutic applications 肝细胞癌中的纳米粒子药物递送系统:靶向策略和治疗应用
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-07-01 DOI: 10.1016/j.onano.2023.100159
Sayali Pravin Metkar , Gasper Fernandes , Prerana D. Navti , Ajinkya N. Nikam , Ritu Kudarha , Namdev Dhas , Raviraja N Seetharam , Krishnan Venkata Santhosh , Bola Sadashiva Satish Rao , Srinivas Mutalik

Hepatocellular carcinoma (HCC) is recognized as a global health issue accounting for millions of deaths every year. Surgery, liver ablation, and embolization therapy are amongst the conventional methods for treatment of HCC. Chemotherapy plays a major role in HCC therapy, however, owing to its conventional pharmacotherapy limitations, it necessitates the development of novel therapeutic strategies. In contrast, nanomedicines for HCC have shown remarkable prospects for solving these complications in HCC owing to their high stability, controlled release, and high drug loading capacity. This review gives an insight into the nano-constructs used for HCC treatment and its active and passive targeting strategies. This review also inculcates the various approaches for targeting the liver cells, its targeting moieties and the conjugation chemistries involved in surface functionalization. A brief description of various therapeutic approaches in the treatment of HCC has also been discussed.

肝细胞癌(HCC)被认为是一个全球性的健康问题,每年造成数百万人死亡。手术、肝消融和栓塞治疗是治疗HCC的常规方法。化疗在HCC治疗中发挥着重要作用,然而,由于其传统药物治疗的局限性,需要开发新的治疗策略。相比之下,纳米药物因其高稳定性、控释和高载药能力,在解决HCC并发症方面显示出令人瞩目的前景。本文综述了用于HCC治疗的纳米结构及其主动和被动靶向策略。本文还介绍了肝细胞靶向的各种方法、靶向基团和参与肝细胞表面功能化的偶联化学。本文还简要介绍了治疗HCC的各种治疗方法。
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引用次数: 3
Exploring the potential of microfluidics for next-generation drug delivery systems 探索微流体技术在新一代药物输送系统中的潜力
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-07-01 DOI: 10.1016/j.onano.2023.100150
Gargi Bhattacharjee , Nisarg Gohil , Malvika Shukla , Swati Sharma , Indra Mani , Alok Pandya , Dinh-Toi Chu , Nhat Le Bui , Yen-Vy Nguyen Thi , Khushal Khambhati , Rupesh Maurya , Suresh Ramakrishna , Vijai Singh

The platform of microfluidics offers a precise control and manipulation over fluids at a small scale and therefore has gained much attention in recent times. This topic is currently applied to automation and high-throughput analysis in several areas, including extraction of DNA, RNA and proteins, gene identification, gene assembly, cloning, single-cell analysis, organs grown on chips, PCR, drug screening, toxicity testing and drug delivery. Conventional methods used for drug delivery are sometimes non-targeted leading to loss of administered drugs and reduced drug effectiveness. Recent advances in microfluidics allow precise dose-dependent delivery of a drug to a targeted location. Several microfluidics designs have been implemented to improve the precision of treatment in clinics. This review highlights currently available tools in microfluidics, designs for drug carriers, delivery methods, robotics and artificial intelligence in the field of microfluidics.

微流体平台提供了在小尺度上对流体的精确控制和操纵,因此近年来受到了广泛关注。目前,该课题已被应用于自动化和高通量分析的多个领域,包括DNA、RNA和蛋白质的提取、基因鉴定、基因组装、克隆、单细胞分析、芯片器官培养、PCR、药物筛选、毒性测试和给药。用于给药的传统方法有时是非靶向性的,导致给药损失和药物有效性降低。微流体技术的最新进展使药物能够根据剂量精确地递送到目标位置。为了提高临床治疗的精度,已经实施了几种微流体设计。本文综述了目前在微流体领域中可用的工具、药物载体设计、给药方法、机器人技术和人工智能。
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引用次数: 1
Wound healing synergy in Wistar albino rats via green synthesized nanoparticles and topical antibiotic neomycin 绿色合成纳米颗粒和局部抗生素新霉素对Wistar白化大鼠伤口愈合的协同作用
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-01 DOI: 10.1016/j.onano.2023.100135
S.V.N. Pammi , Veerabhadhra Swamy Padavala , Taraka Sunil Kumar Karumuri , Chandra Sekhar Kommavari , Manish Shaik , Venkata Ramana Murthy Kolapalli , Lakshmi Kalyani Ruddaraju

Raise of antimicrobial resistance and lack of development in novel antibiotics leads to complications in infection control for wound healing. In perspective to search for best alternatives, antibacterial activity of nanomaterials has shown promising strategy, however concentration dependent toxicity became challenge thereof. In this context, green synthesis protocols of nano materials provide benefits of biocompatibility due to presence of bioactive compounds and also economical with proven efficiency. Further nano-antibiotic combinations may enhance antibacterial efficacy by synergetic action and allows to reduce the dosage of both agents. In the current work, nano-antibiotic gels are prepared using green synthesized nanoparticles (Ag & ZnO NPs) with the combination of antibiotic neomycin and also assessed in-vivo wound healing activity on Wistar albino rats. From the results of the tested formulations, combinational formulations exhibited enhanced and speedier wound contraction (92–96%) with prominent synergetic action when compared with neomycin alone (84%) or nanoparticles alone (82–86%) in a 14-day study. These results demonstrated that green-nano-antibiotic combinational formulations provides prominent avenue to combat the multi drug resistant bacteria without toxicity issue.

抗生素耐药性的提高和新型抗生素的开发缺乏导致伤口愈合感染控制的并发症。从寻找最佳替代品的角度来看,纳米材料的抗菌活性已显示出良好的策略,但浓度依赖性毒性成为其挑战。在这种情况下,纳米材料的绿色合成方案由于生物活性化合物的存在而提供了生物相容性的好处,并且经济且效率已被证明。进一步的纳米抗生素组合可以通过协同作用增强抗菌功效,并允许减少两种药物的剂量。在目前的工作中,纳米抗生素凝胶是用绿色合成纳米颗粒(Ag &氧化锌NPs)与抗生素新霉素联合使用,并评估Wistar白化大鼠的体内伤口愈合活性。从测试配方的结果来看,在一项为期14天的研究中,与单独使用新霉素(84%)或单独使用纳米颗粒(82% - 86%)相比,联合配方表现出增强和更快的伤口收缩(92% - 96%),具有显著的协同作用。这些结果表明,绿色纳米抗生素组合配方为对抗多重耐药细菌提供了一条突出的途径,而且没有毒性问题。
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引用次数: 0
Niosome nanocarrier enhances the ameliorating effects of myrtenol in the lungs of rats with experimental asthma Niosome纳米载体增强月桂醇对实验性哮喘大鼠肺部的改善作用
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-01 DOI: 10.1016/j.onano.2023.100129
Mohammad Amin Rajizadeh , Mohammad Hadi Nematollahi , Elham Jafari , Mohammad Abbas Bejeshk , Mehrnaz Mehrabani , Mohammad Sadegh Razeghinia , Hamid Najafipour

We assessed the anti-inflammatory, anti-oxidative and anti-remodeling impacts of a synthesized myrtenol-loaded niosome in rats with allergic asthma. Forty-nine rats were divided into seven groups of control, vacant niosome (VN), Asthma, Asthma+VN, Asthma+SM (simple myrtenol), Asthma+NM (niosomal myrtenol, 8 mg/kg), and Asthma+B (budesonide, 41 μg). Ovalbumin-induced asthmatic animals were exposed to daily inhalation of drug/vehicle for one week. Histopathology and inflammatory and oxidative stress indices in the lungs were assessed. Myrtenol-loaded niosomes showed appropriate physicochemical properties. Airway smooth muscle thickness, inflammatory cell infiltration, goblet cell hyperplasia, NO, IL-17, and MDA level decreased, and IL-10 and TAC levels increased in tissue and/or BALF of treatment groups. Niosomal myrtenol showed high potency comparable to budesonide in alleviating disease parameters. In conclusion, inhalation of niosomal myrtenol ameliorated inflammation, oxidative stress and tissue remodeling in asthmatic animals more potently than simple myrtenol and could be a target for production of an anti-asthmatic medicine.

我们评估了合成的含有桃金娘烯醇的niosome对过敏性哮喘大鼠的抗炎、抗氧化和抗重塑作用。将49只大鼠分为对照组、空白niosome (VN)、Asthma、Asthma+VN、Asthma+SM(单纯桃金娘烯醇)、Asthma+NM (niosomal myrtenol, 8 mg/kg)、Asthma+B(布地奈德,41 μg) 7组。卵清蛋白诱导的哮喘动物每天吸入药物/媒介物1周。观察肺组织病理学、炎症和氧化应激指标。负载桃金娘烯醇的niosome表现出适当的理化性质。各治疗组气道平滑肌厚度、炎症细胞浸润、杯状细胞增生、NO、IL-17、MDA水平降低,组织和/或BALF中IL-10、TAC水平升高。Niosomal myrtenol在缓解疾病参数方面显示出与布地奈德相当的高效力。综上所述,吸入niosomal myrtenol比单纯的myrtenol更有效地改善哮喘动物的炎症、氧化应激和组织重塑,可能是生产抗哮喘药物的靶点。
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引用次数: 7
Promising synthesized bis (arylmethylidene) acetone -polymeric PCL emulsified nanoparticles with enhanced antimicrobial/antioxidant efficacy: in-vitro and in-vivo evaluation 有前途的合成双(芳基甲基)丙酮-聚合PCL乳化纳米颗粒具有增强的抗菌/抗氧化功效:体外和体内评价
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-01 DOI: 10.1016/j.onano.2023.100139
Sally A. Abou Taleb , Shaymaa Abdalla Ismail , Marwan Mohamed , Reda M. Mourad , Hadeer A. El-Hashemy

Introduction

Recently, bis(arylmethylidene)acetone drugs known as C5-curcumin, were acknowledged for their potent biological effects as a neoteric synthetic alternative to curcumin effectively used to treat many diseases.

Methods

In this study, new polymeric emulsified nanoparticles (PENS) carrying biodegradable polycaprolactone (PCL) polymer moieties within their framework were developed as promising carriers for a modern synthesized bis(arylmethylidene)acetone “(1E,4E)-1,5-di(thiophen-2-yl) penta-1,4dien-3-one” (TPO) with improved bioavailability. Such systems were evaluated by studying their; encapsulation efficiency, release behavior, physicochemical evaluations, TEM and SEM measurements and cytotoxicity, besides the in-vitro and in-vivo biological studies screening.

Results

The results revealed high encapsulation efficiency ranging between 99.31± 2.15 and 99.55 ± 2.03 %, and a sustained release behavior for up to 24 h with nanosized particle size. TPO emulsified nanoparticles (TPO-ENPs) showed effective antimicrobial activity against Candida albicans and Aspergillus brasiliensis as well as antioxidant efficacy with a higher scavenging activity of 177.6μg TE/ mg against free radicals of 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) relatively to the control drug. F1’ and F2’ TPO-ENPs were safe on Vero-cells and proved a significant reduction of hepatocellular alterations and serum ALT levels in control groups.

Conclusion

In conclusion, these novel synthesized TPO-ENPs showed pronounced efficacy as antimicrobial/ antioxidant/ anti-inflammatory/ analgesic/ hepatoprotective therapeutic vehicles.

近年来,被称为c5 -姜黄素的双(芳基甲基)丙酮药物被公认为姜黄素的新合成替代品,具有强大的生物学效应,可有效地用于治疗多种疾病。方法采用新型的聚合物乳化纳米颗粒(PENS),在其框架内携带可生物降解的聚己内酯(PCL)聚合物基团,作为现代合成的双芳基亚甲基丙酮(1E,4E)-1,5-二(噻吩-2-基)五-1,4二烯-3 -1”(TPO)的载体,具有较高的生物利用度。这些系统是通过研究它们的;包封效率,释放行为,理化评价,TEM和SEM测量,细胞毒性,以及体外和体内生物学研究筛选。结果本品包封率为99.31±2.15% ~ 99.55±2.03%,具有纳米级缓释24 h的性能。TPO乳化纳米颗粒(TPO- enps)对白色念珠菌和巴西曲霉具有良好的抑菌活性和抗氧化活性,对2,2-二苯基-1-苯基水合肼(DPPH)自由基的清除率为177.6μg TE/ mg,高于对照药。F1 '和F2 ' TPO-ENPs对vero细胞是安全的,并且在对照组中证明肝细胞改变和血清ALT水平显著降低。结论新合成的TPO-ENPs具有明显的抗菌/抗氧化/抗炎/镇痛/保肝治疗作用。
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引用次数: 2
Corrigendum to ‘Successive cytotoxicity control by evolutionary surface decorated electronic push-pull green ZnCr-LDH nanostructures: Drug delivery enlargement for targeted breast cancer chemotherapy’[OpenNano 8 (2022) 100093] “进化表面修饰的电子推挽绿色ZnCr-LDH纳米结构的连续细胞毒性控制:靶向乳腺癌化疗的药物递送扩大”的更正[OpenNano 8 (2022) 100093]
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-01 DOI: 10.1016/j.onano.2023.100125
Mahsa Kiani , Mojtaba Bagherzadeh , Yousef Fatahi , Hossein Daneshgar , Moein Safarkhani , Ghazal Salehi , Pooyan Makvandi , Mohammad Reza Saeb , Eder C. Lima , Navid Rabiee
{"title":"Corrigendum to ‘Successive cytotoxicity control by evolutionary surface decorated electronic push-pull green ZnCr-LDH nanostructures: Drug delivery enlargement for targeted breast cancer chemotherapy’[OpenNano 8 (2022) 100093]","authors":"Mahsa Kiani ,&nbsp;Mojtaba Bagherzadeh ,&nbsp;Yousef Fatahi ,&nbsp;Hossein Daneshgar ,&nbsp;Moein Safarkhani ,&nbsp;Ghazal Salehi ,&nbsp;Pooyan Makvandi ,&nbsp;Mohammad Reza Saeb ,&nbsp;Eder C. Lima ,&nbsp;Navid Rabiee","doi":"10.1016/j.onano.2023.100125","DOIUrl":"10.1016/j.onano.2023.100125","url":null,"abstract":"","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"11 ","pages":"Article 100125"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43133542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent advances in using liposomes for delivery of nucleic acid-based therapeutics 利用脂质体递送核酸治疗药物的最新进展
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-01 DOI: 10.1016/j.onano.2023.100132
Hamdi Nsairat , Walhan Alshaer , Fadwa Odeh , Ezzaldeen Esawi , Dima Khater , Abeer Al Bawab , Mohamed El-Tanani , Abdalla Awidi , Mohammad S. Mubarak

Nucleic acid therapeutics are rapidly expanding because of recent advancements in production and purification. This class of therapeutics may change the field of disease treatment and personalized medicine since it can cure diseases. However, drug delivery systems are crucial for these therapeutics to fulfill their potential. Liposomes have long been considered ideal platforms for systemic drugs delivery. Considering the development in cancer therapeutics, this work emphases on the current advancements in liposomes’ Nano-formulations, functionalization, and design and how it has been applied to nucleic acid therapeutics. Accordingly, this review covers the literature that deals with liposomes in nucleic acid therapy.

由于最近在生产和纯化方面的进步,核酸治疗正在迅速扩大。这类疗法可能会改变疾病治疗和个性化医疗领域,因为它可以治愈疾病。然而,药物输送系统对于这些疗法发挥其潜力至关重要。脂质体一直被认为是全身给药的理想平台。考虑到癌症治疗的发展,本工作重点介绍了脂质体纳米配方、功能化和设计的最新进展,以及它如何应用于核酸治疗。因此,本文综述了有关脂质体在核酸治疗中的应用的文献。
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引用次数: 7
Nanotheranostics to target antibiotic-resistant bacteria: Strategies and applications 靶向耐药细菌的纳米治疗:策略和应用
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-01 DOI: 10.1016/j.onano.2023.100138
Rahul Bhattacharjee , Arvind Negi , Basudha Bhattacharya , Tanima Dey , Priya Mitra , Subham Preetam , Lamha Kumar , Sulagna Kar , Sabya Sachi Das , Danish Iqbal , Mehnaz Kamal , Fayez Alghofaili , Sumira Malik , Abhijit Dey , Saurabh Kumar Jha , Shreesh Ojha , Ana Cláudia Paiva-Santos , Kavindra Kumar Kesari , Niraj Kumar Jha

Various health agencies, such as the European Medical Agency (EMA), Centers for Disease Control and Prevention (CDC), and World Health Organization (WHO), timely cited the upsurge of antibiotic resistance as a severe threat to the public health and global economy. Importantly, there is a rise in nosocomial infections among covid-19 patients and in-hospitalized patients with the delineating disorder. Most of nosocomial infections are related to the bacteria residing in biofilm, which are commonly formed on material surfaces. In biofilms, microcolonies of various bacteria live in syntropy; therefore, their infections require a higher antibiotic dosage or cocktail of broad-spectrum antibiotics, aggravating the severity of antibiotic resistance. Notably, the lack of intrinsic antibacterial properties in commercial-grade materials desires to develop newer functionalized materials to prevent biofilm formation on their surfaces. To devise newer strategies, materials prepared at the nanoscale demonstrated reasonable antibacterial properties or enhanced the activity of antimicrobial agents (that are encapsulated/chemically functionalized onto the material surface). In this manuscript, we compiled such nanosized materials, specifying their role in targeting specific strains of bacteria. We also enlisted the examples of nanomaterials, nanodevice, nanomachines, nano-camouflaging, and nano-antibiotics for bactericidal activity and their possible clinical implications.

各种卫生机构,如欧洲医疗机构(EMA)、疾病控制和预防中心(CDC)和世界卫生组织(WHO)及时指出,抗生素耐药性的上升是对公共卫生和全球经济的严重威胁。重要的是,covid-19患者和住院患者的医院感染有所上升。大多数医院感染与居住在生物膜中的细菌有关,生物膜通常形成于材料表面。在生物膜中,各种细菌的微菌落以共生性生活;因此,他们的感染需要更高的抗生素剂量或混合使用广谱抗生素,这加剧了抗生素耐药性的严重程度。值得注意的是,商业级材料缺乏固有的抗菌性能,因此需要开发更新的功能化材料来防止其表面形成生物膜。为了设计更新的策略,在纳米尺度上制备的材料显示出合理的抗菌性能或增强抗菌剂的活性(被封装/化学功能化到材料表面)。在这篇论文中,我们编译了这些纳米材料,并详细说明了它们在针对特定菌株的细菌中的作用。我们还列举了纳米材料、纳米器件、纳米机器、纳米伪装和纳米抗生素的杀菌活性及其可能的临床意义。
{"title":"Nanotheranostics to target antibiotic-resistant bacteria: Strategies and applications","authors":"Rahul Bhattacharjee ,&nbsp;Arvind Negi ,&nbsp;Basudha Bhattacharya ,&nbsp;Tanima Dey ,&nbsp;Priya Mitra ,&nbsp;Subham Preetam ,&nbsp;Lamha Kumar ,&nbsp;Sulagna Kar ,&nbsp;Sabya Sachi Das ,&nbsp;Danish Iqbal ,&nbsp;Mehnaz Kamal ,&nbsp;Fayez Alghofaili ,&nbsp;Sumira Malik ,&nbsp;Abhijit Dey ,&nbsp;Saurabh Kumar Jha ,&nbsp;Shreesh Ojha ,&nbsp;Ana Cláudia Paiva-Santos ,&nbsp;Kavindra Kumar Kesari ,&nbsp;Niraj Kumar Jha","doi":"10.1016/j.onano.2023.100138","DOIUrl":"10.1016/j.onano.2023.100138","url":null,"abstract":"<div><p>Various health agencies, such as the European Medical Agency (EMA), Centers for Disease Control and Prevention (CDC), and World Health Organization (WHO), timely cited the upsurge of antibiotic resistance as a severe threat to the public health and global economy. Importantly, there is a rise in nosocomial infections among covid-19 patients and in-hospitalized patients with the delineating disorder. Most of nosocomial infections are related to the bacteria residing in biofilm, which are commonly formed on material surfaces. In biofilms, microcolonies of various bacteria live in syntropy; therefore, their infections require a higher antibiotic dosage or cocktail of broad-spectrum antibiotics, aggravating the severity of antibiotic resistance. Notably, the lack of intrinsic antibacterial properties in commercial-grade materials desires to develop newer functionalized materials to prevent biofilm formation on their surfaces. To devise newer strategies, materials prepared at the nanoscale demonstrated reasonable antibacterial properties or enhanced the activity of antimicrobial agents (that are encapsulated/chemically functionalized onto the material surface). In this manuscript, we compiled such nanosized materials, specifying their role in targeting specific strains of bacteria. We also enlisted the examples of nanomaterials, nanodevice, nanomachines, nano-camouflaging, and nano-antibiotics for bactericidal activity and their possible clinical implications.</p></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"11 ","pages":"Article 100138"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42568567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
PAMAM dendrimers of generation 4.5 loaded with curcumin interfere with α-synuclein aggregation 载姜黄素的第4.5代PAMAM树状大分子干扰α-突触核蛋白聚集
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-01 DOI: 10.1016/j.onano.2023.100140
Daniela E. Igartúa , Florencia González-Lizárraga , Carolina S. Martinez , Silvia del V. Alonso , César L. Ávila , Rosana Chehín , Nadia S. Chiaramoni , M. Jimena Prieto

Curcumin (CUR) is a bioactive compound that has been proposed for the treatment of various neurodegenerative diseases. However, its use is limited due to its low solubility in aqueous media and chemical instability under physiological conditions. Herein, we propose a strategy to overcome these limitations by using PAMAM dendrimers of generation 4.5 (DG4.5). Using a combination of biophysical techniques together with in vitro models, we demonstrate that CUR-DG4.5 complexes: (i) increased the solubility and stability of CUR via internalization into dendrimer's pockets and interaction with terminal carboxylic groups; (ii) showed in vitro biocompatibility and increased CUR uptake; (iii) presented DPPH radical scavenging activity and in vitro inhibition of H2O2-induced stress; and (iv) interfere with α-synuclein aggregation. In conclusion, this work lays the foundation to use curcumin-loaded PAMAM dendrimers of generation 4.5 as nanodrugs capable of reducing oxidative stress and inhibiting α-synuclein aggregation to treat synucleinopathies.

姜黄素(Curcumin, CUR)是一种生物活性化合物,已被提出用于治疗各种神经退行性疾病。然而,由于其在水介质中的溶解度低和生理条件下的化学不稳定性,其使用受到限制。在此,我们提出了一种通过使用第4.5代PAMAM树状大分子(DG4.5)来克服这些限制的策略。结合生物物理技术和体外模型,我们证明了CUR- dg4.5配合物:(i)通过内化到树状大分子的袋和与末端羧基的相互作用,增加了CUR的溶解度和稳定性;(ii)显示出体外生物相容性和增加的CUR摄取;(iii)具有DPPH自由基清除活性和体外抑制h2o2诱导的应激;(4)干扰α-突触核蛋白聚集。综上所述,本研究为利用第4.5代姜黄素负载的PAMAM树状大分子作为能够降低氧化应激和抑制α-突触核蛋白聚集的纳米药物治疗突触核蛋白病奠定了基础。
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引用次数: 2
Binary ethosomes for the enhanced topical delivery and antifungal efficacy of ketoconazole 增强酮康唑局部给药和抗真菌效果的二元酶体
Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-01 DOI: 10.1016/j.onano.2023.100145
Alhanouf A. Aljohani , Maryam A. Alanazi , Lujain A. Munahhi , Jawaher D. Hamroon , Yasmin Mortagi , Mona Qushawy , Ghareb M. Soliman

This work aimed to prepare ketoconazole-loaded ethosomes and binary ethosomes to improve its skin delivery and antifungal efficacy. A 32 factorial design was used to optimize the ethosomes and formulate ketoconazole-loaded binary ethosomes. Ethosomes and binary ethosomes were evaluated for particle size, polydispersity index, zeta potential, percent drug entrapment efficiency, drug release, skin permeation and deposition and antifungal efficacy. The ethosomes particle size ranged from 78.99±16.72 to 321.53±10.41 nm and decreased by increasing phospholipid and ethanol concentrations. The polydispersity index values were in the range of 0.17±0.01 to 0.49 ± 0.04. The percent drug entrapment efficiency ranged from 36.09±2.66 to 95.89±0.19 and increased by increasing phospholipid concentration while ethanol concentration had the opposite effect. The binary ethosomes had smaller size but similar drug entrapment efficiency and zeta potential compared with the ethosomes. They had significantly higher percent drug release (∼96%) and permeation (∼95%) through rat skin compared with the ethosomes (93% and 90%, respectively). Binary ethosomes and ethosomes had, respectively 1.9 and 1.8-fold higher drug skin permeation and 5.3- and 5.6-fold higher drug deposition in the epidermis/dermis compared with the drug suspension. The antifungal efficacy of the drug-loaded ethosomes and binary ethosomes were similar to the drug hydroalcoholic solution. Collectively, these results confirm the potential of these nanocarriers to enhance drug efficacy given their small size, sustained drug release and enhanced skin permeability.

本研究旨在制备酮康唑负载溶酶体和二元溶酶体,以改善其皮肤递送和抗真菌效果。采用32因子设计优化酶体,制备酮康唑负载二元酶体。对脂质体和二元脂质体的粒径、多分散性指数、zeta电位、药物包埋率、药物释放、透皮沉降和抗真菌效果进行评价。脂质体的粒径范围为78.99±16.72 ~ 321.53±10.41 nm,随磷脂和乙醇浓度的增加而减小。多分散性指数范围为0.17±0.01 ~ 0.49±0.04。药物包封率在36.09±2.66 ~ 95.89±0.19之间,随磷脂浓度的增加而增加,而乙醇浓度则相反。二元质体体积较小,但药物包封效率和zeta电位相近。与脂质体(分别为93%和90%)相比,它们通过大鼠皮肤的药物释放率(~ 96%)和渗透率(~ 95%)显著更高。与药物悬浮液相比,双溶体和溶体的药物透皮率分别高1.9倍和1.8倍,表皮/真皮沉积量分别高5.3倍和5.6倍。载药酶体和二元酶体的抗真菌效果与药物氢醇溶液相似。总的来说,这些结果证实了这些纳米载体的潜力,因为它们体积小,药物持续释放和增强皮肤渗透性。
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引用次数: 6
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