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Mesothelin-Mediated Paclitaxel Phase-Shifted Nanodelivery System for Molecular Ultrasound Imaging and Targeted Therapy Potential in Ovarian Cancer. 间皮素介导的紫杉醇相移纳米给药系统用于卵巢癌的分子超声成像和靶向治疗。
Pub Date : 2024-06-05 DOI: 10.2174/0115672018300502240530064139
Yujie Wan, Li Luo, Xinzhi Xu, Qihuan Fu, Ying Li, Kaifeng Huang, Hang Zhou, Fang Li

Background: Ovarian cancer presents a substantial risk to women's health and lives, with early detection and treatment proving challenging. Targeted nanodelivery systems are viewed as a promising approach to enhance the effectiveness of ovarian cancer treatment and ultrasonic imaging outcomes.

Objective: A phase-shifted nanodelivery system (NPs) loaded with paclitaxel (PTX) and further conjugated with avidin (Ab) was studied, with the goal of investigating the effects of targeted nanodelivery strategies on the in vitro therapeutic efficacy and ultrasonic imaging of ovarian cancer. This study provides a foundation for future in vivo treatments utilizing this approach.

Methods: PTX-NPs were prepared using the single water-in-oil (O/W) emulsion solvent evaporation method, with avidin coupling achieved through biotin-avidin affinity. The encapsulation efficiency and release profile of PTX were analyzed using UV spectrophotometry. The phase-shift properties of the Ab-PTX-NPs delivery system were evaluated, and the targeting efficiency, cytotoxicity against SKOV3 cells, and in vivo biosafety of various nanodelivery systems were assessed.

Results: The prepared nanodelivery system showed a stable and uniform structure with a good particle size distribution and exhibited favorable release characteristics under ultrasound exposure. In vitro experiments revealed that the nanodelivery system displayed excellent targeting and cytotoxic effects against SKOV3 cells, indicating the potential of the Ab-PTX-NPs delivery system for targeted ovarian cancer therapy. In vivo safety studies demonstrated the high biosafety of the prepared nanodelivery system.

Conclusion: A novel nanodelivery system was developed, and the experimental results obtained provide a solid experimental basis for further research on in vivo ultrasound molecular imaging technology, offering new insights into targeted ultrasound molecular imaging and the treatment of ovarian cancer.

背景:卵巢癌对妇女的健康和生命构成巨大风险,早期检测和治疗具有挑战性。靶向纳米给药系统被认为是提高卵巢癌治疗效果和超声波成像结果的一种有前途的方法:研究了一种负载紫杉醇(PTX)并进一步与阿维丁(Ab)共轭的相移纳米给药系统(NPs),旨在探讨靶向纳米给药策略对卵巢癌体外疗效和超声成像的影响。这项研究为未来利用这种方法进行体内治疗奠定了基础:方法:采用单一油包水(O/W)乳液溶剂蒸发法制备 PTX-NPs,并通过生物素-阿维蛋白亲和力实现阿维蛋白偶联。采用紫外分光光度法分析了 PTX 的包封效率和释放曲线。评价了 Ab-PTX-NPs 给药系统的相移特性,并评估了各种纳米给药系统的靶向效率、对 SKOV3 细胞的细胞毒性和体内生物安全性:结果:制备的纳米给药系统结构稳定均匀,粒度分布良好,在超声暴露下表现出良好的释放特性。体外实验显示,该纳米给药系统对SKOV3细胞具有良好的靶向性和细胞毒性作用,表明Ab-PTX-NPs给药系统具有卵巢癌靶向治疗的潜力。体内安全性研究表明所制备的纳米给药系统具有很高的生物安全性:结论:该研究开发了一种新型纳米给药系统,其实验结果为进一步研究体内超声分子成像技术提供了坚实的实验基础,为靶向超声分子成像和卵巢癌治疗提供了新的思路。
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引用次数: 0
Niosome-Based Hydrogel of Quince Extract: A Promising Strategy for Expedited Full-thickness Wound Healing in Rat. 基于榅桲提取物的水凝胶:加速大鼠全厚伤口愈合的有效策略
Pub Date : 2024-06-04 DOI: 10.2174/0115672018282735240528072715
Pedram Ebrahimnejad, Paria Fadaee Heydarabadi, Fereshteh Talebpour Amiri, Fatemeh Mirzaee, Melika Ahmadi, Somayeh Shahani

Background: The regeneration of tissue damage involves a series of molecular and cellular events that can be mediated by various natural compounds. Recent studies have highlighted the anti-inflammatory, anti-ulcer, and skin-protecting properties of Cydonia oblonga (Quince), which are mainly attributed to phenolic compounds. These compounds may have some drawbacks when targeting wound applications, including low bioavailability at the wound site. Moreover, to overcome these limitations, surfactant-based nanovesicular systems have been developed as carriers of such compounds for wound healing.

Objective: This study aimed to highlight the possible therapeutic potential of niosome-based hydrogel from Quince extract to stabilize and deliver the related bioactive compounds to full-thickness wounds in rats.

Methods: The niosomal hydrogel was prepared using a thin-film hydration method with the fruit extract (70% methanol). The formulation was optimized by evaluating size, zeta potential, dispersion index, and drug encapsulation efficiency. Full-thickness wounds were created on the dorsal cervical area of Wistar rats, and histopathological analysis of biopsy specimens was conducted on the 12th day of treatment.

Results: Under the study conditions, niosomal hydrogel displayed good physicochemical stability. Histopathological findings demonstrated that niosomal gel promoted angiogenesis, fibroblast maturation, collagen deposition, keratinization, and epidermal layer formation more effectively than control and hydrogel base. Furthermore, niosomal gel treatment markedly reduced inflammation. The total phenol concentration was determined to be 13.34 ± 0.90 mg gallic acid equivalents per gram of dried extract.

Conclusion: The niosomal hydrogel containing C. oblonga extract shows potential as a novel approach for wound healing, warranting further investigation in this field.

背景:组织损伤的再生涉及一系列分子和细胞事件,这些事件可由各种天然化合物介导。最近的研究强调了榅桲(Cydonia oblonga)的抗炎、抗溃疡和皮肤保护特性,这些特性主要归因于酚类化合物。这些化合物在针对伤口应用时可能存在一些缺点,包括在伤口部位的生物利用率较低。此外,为了克服这些局限性,人们开发了基于表面活性剂的纳米囊泡系统,作为此类化合物的载体,用于伤口愈合:本研究旨在强调从榅桲提取物中提取的基于niosome的水凝胶可能具有的治疗潜力,以稳定相关生物活性化合物并将其输送到大鼠的全厚伤口中:方法:采用薄膜水合法,用榅桲提取物(70%甲醇)制备榅桲水凝胶。通过评估尺寸、ZETA电位、分散指数和药物封装效率,对配方进行了优化。在 Wistar 大鼠的颈背部位造成全厚伤口,并在治疗的第 12 天对活检标本进行组织病理学分析:结果:在研究条件下,水凝胶具有良好的理化稳定性。组织病理学研究结果表明,与对照组和水凝胶基质相比,尼泊金凝胶能更有效地促进血管生成、成纤维细胞成熟、胶原沉积、角质化和表皮层形成。此外,尼索米尔凝胶还能明显减轻炎症反应。经测定,每克干燥提取物的总酚浓度为 13.34 ± 0.90 毫克没食子酸当量:含有 C. oblonga 提取物的透明质水凝胶显示出作为伤口愈合新方法的潜力,值得在该领域开展进一步研究。
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引用次数: 0
Recent Advancement of Nanotheranostics in Cancer Applications. 纳米otheranostics 在癌症应用中的最新进展。
Pub Date : 2024-05-29 DOI: 10.2174/0115672018307617240514092110
Suphiya Parveen, R Abira, Safal Paikray, Liza Sahoo, Nigam Sekahr Tripathy, Fahima Dilnawaz

The field of nanomedicine shows promising implications in the concurrent delivery of therapeutic and diagnostic (theranostics) compounds in a single platform. Nanotheranostics is incredibly promising since it offers simultaneous non-invasive disease detection and treatment together with the exciting ability to track drug release and distribution in real-time, thereby forecasting and evaluating the efficacy of the therapy. The cancer theranostic approach improves the cancer prognosis safely and effectively. Common classes of nanoscale biomaterials, including magnetic nanoparticles, quantum dots, upconversion nanoparticles, mesoporous silica nanoparticles, carbon- based nanoparticles, and organic dye-based nanoparticles, have demonstrated enormous potential for theranostic activity. The need for improved disease detection and enhanced chemotherapeutic treatments, together with realistic considerations for clinically translatable nanomaterials will be key driving factors for theranostic agent research shortly. The developments of precision theranostic nanomaterials are employed in imaging systems like, MRI, PET, and SPECT with multifunctional ability. In this review, different nanoparticles/nanomaterials that are used/developed for theranostic activity are discussed.

纳米医学领域显示出在单一平台上同时提供治疗和诊断(治疗)化合物的广阔前景。纳米治疗学具有令人难以置信的前景,因为它能同时进行非侵入性疾病检测和治疗,并能实时跟踪药物的释放和分布,从而预测和评估疗效。癌症治疗方法能安全有效地改善癌症预后。磁性纳米粒子、量子点、上转换纳米粒子、介孔二氧化硅纳米粒子、碳基纳米粒子和有机染料基纳米粒子等常见的纳米级生物材料已显示出巨大的治疗活性潜力。改善疾病检测和提高化疗效果的需求,以及对可临床转化的纳米材料的现实考虑,将成为近期治疗剂研究的关键驱动因素。精确治疗纳米材料的开发应用于成像系统,如具有多功能能力的 MRI、PET 和 SPECT。本综述讨论了用于/开发治疗活性的不同纳米颗粒/纳米材料。
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引用次数: 0
Limitations and Innovative Application Methods of Surfactants for Solubilization of Poorly Water-Soluble Drugs. 表面活性剂在溶解水溶性差的药物方面的局限性和创新应用方法。
Pub Date : 2024-05-29 DOI: 10.2174/0115672018299592240524074005
Gang Jin, Jie Wang, Jie Xu, Qing Jin, Jian-Fei Xue, Lin-Han Li

Poor solubility of drugs leads to poor bioavailability and therapeutic efficiency. A large proportion of drugs that are not developed and marketed for use by patients are due to their extremely low solubility. Therefore, improving the solubility of poorly water-soluble drugs is one of the most important aspects of the field of drug research. With the continuous development of more and more formulation techniques and excipient applications, the solubility of poorly water-soluble drugs can be improved to a certain extent to obtain better pharmacokinetics and pharmacodynamics, including pH microenvironment regulation technology, inclusion complex, solid dispersion, nanotechnology, and application of surfactants. However, the most widely used among them is the application of surfactants. This technique can reduce the surface tension, improve wettability, and have a remarkable solubilizing ability after forming micelles. However, surfactants have also been found to possess certain limitations in solubilization. In this review, the factors affecting the solubilization of surfactants and limiting their application have been summarized from several aspects. These factors include drugs, additives, and media. Some ideas to solve these application limitations have also been put forward, which can lay a foundation for the wider application of surfactants in the future.

药物溶解度低会导致生物利用率和治疗效率低下。很大一部分未被开发和上市供患者使用的药物就是因为其溶解度极低。因此,提高水溶性差的药物的溶解度是药物研究领域最重要的方面之一。随着越来越多制剂技术和辅料应用的不断发展,包括 pH 微环境调节技术、包合络合物、固体分散技术、纳米技术和表面活性剂的应用等,都可以在一定程度上改善水溶性差的药物的溶解度,从而获得更好的药代动力学和药效学。但其中应用最广泛的是表面活性剂的应用。这种技术可以降低表面张力,改善润湿性,形成胶束后具有显著的增溶能力。然而,人们也发现表面活性剂在增溶方面有一定的局限性。本综述从几个方面总结了影响表面活性剂增溶和限制其应用的因素。这些因素包括药物、添加剂和介质。同时也提出了一些解决这些应用限制的思路,为今后表面活性剂的更广泛应用奠定了基础。
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引用次数: 0
Three-Dimensional Printing Technology for Medicines. 药品三维打印技术。
Pub Date : 2024-05-22 DOI: 10.2174/0115672018318133240520093550
Clara Dias de Castro Moreira da Silva, Ana Paula Matos, Beatriz Hecht Ortiz, Alessandra Lifsitch Viçosa, Eduardo Ricci-Junior
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引用次数: 0
Ufosomes as Topical/Transdermal Drug Delivery System: Structural Components, Preparation Techniques and Therapeutic Application. 作为局部/透皮给药系统的超微体:结构成分、制备技术和治疗应用。
Pub Date : 2024-05-22 DOI: 10.2174/0115672018302045240510114907
Sumayah Al-Mahmood, Nawal Rajab Ayash

Fatty acid vesicles, or ufasomes, are spherical structures that encapsulate and deliver bioactive molecules to the skin or other tissues. They are formed from both saturated and unsaturated fatty acids and offer advantages over liposomes, including greater stability and a wider range of pH compatibility. They are composed of two layers of fatty acid molecules with their hydrocarbon tails facing inwards and their carboxylic groups facing outwards. The space between the two layers is filled with surfactants. There are various methods for characterizing and evaluating the properties of vesicles and drug-loaded vesicles, such as differential scanning calorimetry (DSC), Electron microscopy, UV-visible spectrophotometry, Dialysis, Franz diffusion cell, and stability testing. Each method provides specific information about the vesicles, such as their size, zeta potential, morphology, drug content, entrapment efficiency, drug release, permeability, and stability. Ufasomes have potential applications in topical/transdermal drug delivery as food additives, cosmetics, vaccines, gene therapy vectors, and diagnostic tools. Their ability to encapsulate and deliver bioactive molecules makes them valuable in various fields, including drug delivery and biomedical research. In summary, fatty acid vesicles represent a versatile drug delivery system with potential applications in various fields.

脂肪酸囊泡或 ufasomes 是一种球形结构,可封装生物活性分子并将其输送到皮肤或其他组织。它们由饱和脂肪酸和不饱和脂肪酸组成,与脂质体相比具有更高的稳定性和更广泛的 pH 相容性等优点。它们由两层脂肪酸分子组成,烃基尾部朝内,羧基朝外。两层分子之间的空隙由表面活性剂填充。有多种方法可以表征和评估囊泡和药物负载囊泡的特性,如差示扫描量热法(DSC)、电子显微镜、紫外-可见分光光度法、透析法、弗朗兹扩散池和稳定性测试。每种方法都能提供囊泡的具体信息,如大小、ZETA电位、形态、药物含量、包埋效率、药物释放、渗透性和稳定性。超微结构体具有作为食品添加剂、化妆品、疫苗、基因治疗载体和诊断工具用于局部/透皮给药的潜力。它们封装和输送生物活性分子的能力使其在包括药物输送和生物医学研究在内的各个领域都具有重要价值。总之,脂肪酸囊泡是一种多功能的药物输送系统,在各个领域都有潜在的应用前景。
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引用次数: 0
Structures, Stability, and Cellular Uptake of Protein Nanoparticles (NP) and Extracellular Vesicles (EVs). 蛋白质纳米颗粒 (NP) 和细胞外囊泡 (EV) 的结构、稳定性和细胞吸收。
Pub Date : 2024-05-14 DOI: 10.2174/0115672018314957240508073903
Olga Morozova, Polina Golubinskaya, Ekaterina Obraztsova, Artem Eremeev, Dmitry Klinov
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引用次数: 0
A Biodegradable Nano-Drug Delivery Platform for Co-Delivery of Minocycline and Chitosan to Achieve Efficient and Safe Non-Surgical Periodontitis Therapy. 一种可生物降解的纳米给药平台,用于米诺环素和壳聚糖的联合给药,实现高效安全的非手术牙周炎治疗。
Pub Date : 2024-05-03 DOI: 10.2174/0115672018305286240502060504
Jinxin Yang, Jie Mou, Kexin Ding, Shaoyue Zhu, Zhe Sun, Yawen Cui, Sihan Meng, Guowei Qiang, Weisen Zhong, Zongxiang Liu

Introduction: Mesoporous silica nanoparticles (MSN) are widely used as ideal nanovehicles for the delivery of chemotherapeutic drugs. However, the balance between high anti-periodontitis activity and low biotoxicity has been challenging to maintain in most relevant studies owing to the slow degradation of silica in living organisms.

Method: In this study, -responsive hydroxyapatite (HAP) was doped into the MSN skeleton, and the chemotherapeutic drug minocycline hydrochloride (MH) was loaded into the pores of MSN, forming a negatively charged drug delivery system. Cationic chitosan (COS) is a biodegradable material with high antibacterial performance and good biosafety. In this study, COS was immobilized on the surface of the drug-loaded particles through stable charge interaction to construct a composite drug delivery system (MH@MSNion@COS).

Results: In vitro and cellular experiments demonstrated effective degradation of the nanocarrier system and synchronized controlled release of the drug. Notably, compared with single MH administration, this system, in which MH and COS jointly regulated the expression levels of periodontitis- associated inflammatory factors (TNF-α, IL-6, IL-1β, and iNOS), better inhibited the progress of periodontitis and induced tissue regeneration without showing significant toxic side effects in cells.

Conclusion: This system provides a promising strategy for the design of intelligent, efficient, and safe anti-periodontitis drug delivery systems.

导言:介孔二氧化硅纳米颗粒(MSN)作为理想的纳米载体被广泛应用于化疗药物的输送。然而,由于二氧化硅在生物体内降解缓慢,在大多数相关研究中保持高抗牙周炎活性和低生物毒性之间的平衡一直是个挑战:本研究将响应性羟基磷灰石(HAP)掺杂到MSN骨架中,将化疗药物盐酸米诺环素(MH)负载到MSN孔隙中,形成带负电荷的给药系统。阳离子壳聚糖(COS)是一种可生物降解的材料,具有很高的抗菌性能和良好的生物安全性。本研究通过稳定的电荷相互作用将 COS 固定在载药颗粒表面,构建了一种复合给药系统(MH@MSNion@COS):体外实验和细胞实验表明,纳米载药系统能有效降解药物并同步控制药物释放。值得注意的是,与单一的 MH 给药相比,该系统中 MH 和 COS 共同调节牙周炎相关炎症因子(TNF-α、IL-6、IL-1β 和 iNOS)的表达水平,能更好地抑制牙周炎的进展并诱导组织再生,同时不会对细胞产生明显的毒副作用:该系统为设计智能、高效、安全的抗牙周炎给药系统提供了一种可行的策略。
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引用次数: 0
Preparation, Characterization, and Hepatoprotective Activity Evaluation of Quercetin-loaded Pluronic® F127/Chitosan-Myristic Acid Mixed Micelles. 载槲皮素的 Pluronic® F127/壳聚糖-肉豆蔻酸混合胶束的制备、表征和肝保护活性评估
Pub Date : 2024-03-18 DOI: 10.2174/0115672018278618240304054731
Darshan R Telange, Seema Kamdi, Atul T Hemke, Anil M Pethe, Vijay B Lambole, Umesh B Telrandhe

Background: Quercetin (QTN) is a flavonol antioxidant found in foods, medicinal plants, fruits, vegetables, and beverages. QTN oral consumption produces several biological effects, including antioxidant, cardioprotective, anti-apoptotic, anti-cancer, neuroprotection, anti-hypertensive, and chemo preventive.

Objective: The study aimed to prepare Pluronic®F127/chitosan-myristic acid copolymer (PF127/C-MAc)-based mixed micelles (QTN MM) to improve the biopharmaceutical and hepatoprotective potential of QTN.

Methods: QTN MM was developed employing thin-film hydration and optimized using full factorial design (FFD). Optimized QTN MM was analyzed using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), powder x-ray diffractometry (PXRD), in vitro dissolution, ex vivo permeation, and in vivo antioxidant activity in carbon tetrachloride (CCL4)-induced albino rats.

Results: PF127/C-MAc ratio (1:1) with CMC value ~ 5 μg/mL showed the suitability for MM. Characterization supported the formation of MM. QTN MM revealed prominent encapsulation efficiency and drug loading of about ~ 95.10% and ~ 12.28% w/w, respectively. MM spherical shape of QTN with a smaller particle size of ~ 34.08 nm and a higher zeta potential of ~ 36.24 nm indicated excellent physical stability. Dissolution and ex vivo permeation results revealed higher dissolution and permeation of QTN MM compared to QTN and PM. In vivo antioxidant activity suggested that QTN MM at (~ 20 mg/kg, p.o.) restored the enhanced marker enzyme level compared to QTN.

Conclusion: The findings demonstrate that developed QTN MM could be used as an alternative nanocarrier to increase the biopharmaceutical and hepatoprotective potential of QTN and other flavonoids.

背景:槲皮素(QTN)是一种存在于食物、药用植物、水果、蔬菜和饮料中的黄酮醇类抗氧化剂。口服槲皮素可产生多种生物效应,包括抗氧化、保护心脏、抗细胞凋亡、抗癌、神经保护、抗高血压和预防化疗:本研究旨在制备基于 Pluronic®F127/ 壳聚糖-肉豆蔻酸共聚物(PF127/C-MAc)的混合胶束(QTN MM),以提高 QTN 的生物制药和保肝潜力:方法:采用薄膜水合技术开发了 QTN MM,并利用全因子设计(FFD)对其进行了优化。采用扫描电子显微镜(SEM)、差示扫描量热仪(DSC)、傅立叶变换红外光谱(FT-IR)、粉末 X 射线衍射仪(PXRD)对优化后的 QTN MM 进行了分析,并对四氯化碳(CCL4)诱导的白化大鼠进行了体外溶解、体内渗透和体内抗氧化活性分析:结果表明:PF127/C-MAc 的比例为 1:1,CMC 值约为 5 μg/mL,适用于 MM。表征支持 MM 的形成。QTN MM 的包封效率和载药量分别约为 95.10%和 12.28%(重量百分比)。QTN MM 呈球形,粒径较小,约为 34.08 nm,zeta 电位较高,约为 36.24 nm,这表明其具有良好的物理稳定性。溶解和体内渗透结果表明,与 QTN 和 PM 相比,QTN MM 的溶解度和渗透度更高。体内抗氧化活性表明,与 QTN 相比,QTN MM(~ 20 mg/kg,p.o.)可恢复增强的标记酶水平:研究结果表明,开发的 QTN MM 可用作替代纳米载体,以提高 QTN 和其他黄酮类化合物的生物制药和保肝潜力。
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引用次数: 0
Recent Trends and Applications of Nanostructure-based Drug Delivery in Alleviating Chronic Obstructive Pulmonary Disease (COPD). 基于纳米结构的药物输送在缓解慢性阻塞性肺病 (COPD) 方面的最新趋势和应用。
Pub Date : 2024-03-05 DOI: 10.2174/0115672018289883240226113353
Lokesh Nagar, Nisha Gulati, Annu Saini, Sachin Singh, Gaurav Gupta, Ronan MacLoughlin, Dinesh Kumar Chellappan, Kamal Dua, Harish Dureja

Chronic Obstructive Pulmonary Disease (COPD), a chronic lung disease that causes breathing difficulties and obstructs airflow from the lungs, has a significant global health burden and affects millions of people worldwide. The use of pharmaceuticals in COPD treatment is aimed to alleviate symptoms, improve lung function, prevent exacerbations, and enhance the overall quality of life for patients. Nanotechnology holds great promise to alleviate the burden of COPD. The main goal of this review is to present the full spectrum of therapeutics based on nanostructures for the treatment and management of COPD, including nanoparticles, polymeric nanoparticles, polymeric micelles, solid-lipid nanoparticles, liposomes, exosomes, nanoemulsions, nanosuspensions, and niosomes. Nanotechnology is just one of the many areas of research that may contribute to the development of more effective and personalized treatment modalities for COPD patients in the future. Future studies may be focused on enhancing the therapeutic effectiveness of nanocarriers by conducting extensive mechanistic investigations to translate current scientific knowledge for the effective management of COPD with little or no adverse effects.

慢性阻塞性肺病(COPD)是一种会导致呼吸困难和肺部气流受阻的慢性肺部疾病,对全球健康造成重大负担,影响着全球数百万人。在慢性阻塞性肺病治疗中使用药物的目的是减轻症状、改善肺功能、防止病情恶化并提高患者的整体生活质量。纳米技术在减轻慢性阻塞性肺病的负担方面大有可为。本综述的主要目的是全面介绍基于纳米结构的慢性阻塞性肺病治疗和管理疗法,包括纳米颗粒、聚合物纳米颗粒、聚合物胶束、固脂纳米颗粒、脂质体、外泌体、纳米乳液、纳米悬浮液和niosomes。纳米技术只是众多研究领域中的一个,未来可能有助于为慢性阻塞性肺病患者开发更有效、更个性化的治疗模式。未来的研究重点可能是通过开展广泛的机理研究来提高纳米载体的治疗效果,从而将现有的科学知识转化为有效治疗慢性阻塞性肺病的方法,同时减少或避免不良反应。
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引用次数: 0
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Current drug delivery
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