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Self-Emulsifying Drug Delivery System (SEDDS): An Emerging Dosage Form to Improve the Bioavailability of Poorly Absorbed Drugs. 自乳化给药系统(SEDDS):一种提高吸收不良药物生物利用度的新剂型。
IF 2.7 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2020-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2020033111
Sonia Singh, Meenakshi Bajpai, Pradeep Mishra

The main objective of drug(s) formulation is to enhance the bioavailability of the drug within the body. Some of the challenging issues associated with poorly water-soluble drugs concern solubility and bioavailability factors. To overcome these problems, new technologies, such as lipid-based drug delivery systems including micro or nano emulsifying drug delivery system, have gained importance in recent years, due to their enhanced solubility and bioavailability in the gastrointestinal tract. Such systems are incorporated or solubilized within the lipid excipients or mixed with oils or surfactants/co-solvents to facilitate the solubility and absorption rate, which can enhance the bioavailability of the targeted drug. This review provides a comprehensive summary about the properties, factors affecting formulations, excipients, formulation techniques, and characterization of self-emulsifying drug delivery systems. It also focuses on the new approaches concerned with SEDDS.

药物制剂的主要目的是提高药物在体内的生物利用度。与水溶性差的药物相关的一些具有挑战性的问题涉及溶解度和生物利用度因素。为了克服这些问题,近年来以脂质为基础的药物传递系统(包括微纳米乳化药物传递系统)因其在胃肠道中的溶解度和生物利用度提高而变得越来越重要。这样的系统被掺入或溶解在脂质赋形剂中,或与油或表面活性剂/助溶剂混合,以促进溶解度和吸收率,从而可以增强靶向药物的生物利用度。本文综述了自乳化给药系统的性质、影响配方的因素、赋形剂、配方技术和表征。它还侧重于与SEDDS有关的新方法。
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引用次数: 8
Reassessment of Therapeutic Applications of Carbon Nanotubes: A Majestic and Futuristic Drug Carrier. 碳纳米管治疗应用的再评估:一种宏伟和未来的药物载体。
IF 2.7 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2020-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2020032570
Bharti Mangla, Shamama Javed, Kanchan Kohli, Aarif Ahsan, Waquar Ahsan

Carbon nanotubes (CNTs) have been identified as one of the most advanced and versatile nanovectors, theranostics, and futuristic drug delivery tools for highly effective delivery of genes, drugs, and biomolecules, as well as for use in bioimaging and as biosensors. CNTs have drawn tremendous attention and interest from researchers worldwide in the past two decades owing to a number of unique characteristics including well defined physicochemical properties, large surface area, in addition to exclusive electrical and optical properties. Numerous recent literature related to the design and applications of CNTs were studied and summarized accordingly. Special emphasis was given for the applications of CNTs in drug targeting. Specific targeting of anticancer drugs such as cisplatin, doxorubicin, taxol, gemcitabine, and methotrexate, and delivery of small interfering RNA, micro-RNA, as well as plasmid DNA have been successfully assisted using CNTs. All the major applications of CNTs were summarized in detail with possible toxicity concerns associated with them. As far as their toxicity is concerned, it was noticed that the functionalized CNTs pose little toxicity and do not have immunogenic effects. In conclusion, CNTs showed great potential in developing a new generation of carriers for various drugs and related biomolecules. The application of CNTs ranges from physics to chemistry and now they are expanding their roles in the therapeutic drug delivery in the modern healthcare system. With applications in every imaginable route of administration, CNTs bring therapeutic benefits to society. The pharmaceutical, biopharmaceutical, pharmacokinetic, pharmacodynamic, and clinical efficacy of CNTs is explored in detail in this review.

碳纳米管(CNTs)已被确定为最先进和通用的纳米载体之一,治疗学和未来的药物递送工具,用于高效地递送基因,药物和生物分子,以及用于生物成像和生物传感器。在过去的二十年中,碳纳米管由于具有明确的物理化学性质、较大的表面积以及独特的电学和光学性质等一系列独特的特性,引起了全世界研究人员的极大关注和兴趣。本文对近年来大量与碳纳米管的设计和应用相关的文献进行了研究和总结。特别强调了碳纳米管在药物靶向中的应用。抗癌药物如顺铂、阿霉素、紫杉醇、吉西他滨和甲氨蝶呤的特异性靶向,以及小干扰RNA、微RNA和质粒DNA的递送已经成功地使用了碳纳米管。详细总结了碳纳米管的所有主要应用及其可能的毒性问题。就其毒性而言,我们注意到功能化的碳纳米管毒性很小,不具有免疫原性作用。综上所述,CNTs在开发各种药物和相关生物分子的新一代载体方面具有很大的潜力。碳纳米管的应用范围从物理到化学,现在它们正在扩大其在现代医疗保健系统中治疗性药物输送中的作用。CNTs应用于各种可想象的给药途径,为社会带来治疗益处。本综述详细探讨了碳纳米管的药学、生物药学、药代动力学、药效学和临床疗效。
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引用次数: 2
Polysaccharides against Viruses: Immunostimulatory Properties and the Delivery of Antiviral Vaccines and Drugs. 抗病毒多糖:免疫刺激特性和抗病毒疫苗和药物的递送。
IF 2.7 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2020-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2019027229
Guy-Alain Junter, Carole Karakasyan

Because viruses still represent a significant threat to human and animal health worldwide, the development of effective weapons against viral infections remains a top priority for the biopharmaceutical industry. This article reviews the dietary and pharmaceutical applications of polysaccharides (PS), first of all chitosan, in the prevention and treatment of viral diseases, focusing more particularly on solid or gel micro/nanoparticulate systems. The intrinsic antiviral activity of PS and their immunostimulatory effects, implemented in animal and human diets, are first surveyed. Then the review discusses the potential of PS-based particles as carriers of antiviral drugs and vaccines, with emphasis on the adjuvant potency of PS in solid vaccine formulations. The gap between the abundance of academic studies in this area and the lack of actual antiviral formulations dispensed to human patients is underlined, notwithstanding a number of branded products on the market.

由于病毒在世界范围内仍然对人类和动物健康构成重大威胁,因此开发对抗病毒感染的有效武器仍然是生物制药行业的首要任务。本文综述了多糖(PS),首先是壳聚糖,在预防和治疗病毒性疾病方面的饮食和药物应用,重点介绍了固体或凝胶微/纳米颗粒系统。本文首次调查了PS内在的抗病毒活性及其在动物和人类饲料中的免疫刺激作用。然后讨论了基于PS的颗粒作为抗病毒药物和疫苗载体的潜力,重点介绍了PS在固体疫苗制剂中的佐剂效力。尽管市场上有许多品牌产品,但这一领域学术研究的丰富与实际配给人类患者的抗病毒配方的缺乏之间的差距是突出的。
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引用次数: 7
Nanoparticles as Adjuvants in Vaccine Delivery. 纳米颗粒作为疫苗递送佐剂。
IF 2.7 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2020-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2020033273
Anuj Garg, Hitesh Kumar Dewangan

Nanotechnology provides an excellent platform for the development of a new generation of vaccines. These are based on purified subunit proteins or polysaccharides, recombinant proteins, synthetic peptides, or nucleic acids. These types of vaccines may be insufficiently immunogenic, thus requiring adjuvants that augment their immunogenicity. Nanoparticles (NPs) can act as adjuvants for vaccines, hence they are referred to as a nano-adjuvant (NA). NPs can either encapsulate or adsorb the vaccine antigen or DNA in an appropriate formulation, thus increasing stability, cellular uptake, and immunogenicity. In addition, the biodistribution and systemic release of a vaccine can also be controlled by different NA formulations. This review provides an overview of the classification of NAs and also addresses factors influencing the stability, release, and immunogenicity of the formulated vaccine. A basic understanding of these factors enables a more rational design of NA formulations. Applications of NAs and key challenges in their formulation development are also discussed.

纳米技术为开发新一代疫苗提供了一个极好的平台。这些是基于纯化的亚基蛋白或多糖、重组蛋白、合成肽或核酸。这些类型的疫苗可能免疫原性不足,因此需要佐剂来增强其免疫原性。纳米颗粒(NPs)可以作为疫苗佐剂,因此它们被称为纳米佐剂(NA)。NPs可以包封或以适当的配方吸附疫苗抗原或DNA,从而增加稳定性、细胞摄取和免疫原性。此外,疫苗的生物分布和全身释放也可以通过不同的NA配方来控制。本文综述了NAs的分类,并讨论了影响配方疫苗稳定性、释放性和免疫原性的因素。对这些因素的基本了解有助于更合理地设计NA配方。讨论了NAs的应用及其配方开发中的关键挑战。
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引用次数: 22
Recent Advances in Herbal Drug Nanocarriers against Cervical Cancer 中药纳米载体抗宫颈癌研究进展
IF 2.7 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2020-01-01 DOI: 10.1615/critrevtherdrugcarriersyst.2020034170
M. Damani, Krishna Baxi, C. Aranha, S. Sawarkar
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引用次数: 5
A Review on Applications of Vitamin B12 as Therapeutic Carrier in Drug Delivery 维生素B12作为治疗性载体在药物传递中的应用综述
IF 2.7 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2020-01-01 DOI: 10.1615/critrevtherdrugcarriersyst.2020034305
R. Garg, Anuj Garg
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引用次数: 0
Long-Acting Injectables: Current Perspectives and Future Promise. 长效注射剂:当前的观点和未来的前景。
IF 2.7 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2018025649
Komal Chaudhary, Mayur M Patel, Priti J Mehta

The parenteral route of administration is preferred over the oral route for treatment of many chronic and life-threatening diseases due to better patient compliance. Long-acting injectables/depot delivery systems are formulations intended for prolonged/sustained drug release over a long period of time ranging from a few days to months. Depot delivery systems enhance product quality by decreasing dosing frequency, simplifying the drug regimen. Parenteral depots reduce the relapse rate of disease and the maintenance phase of therapy, hence improving efficacy and treatment adherence. However, despite being extensively explored in the last seventy years, only a few depot products have been marketed or have reached commercial viability. The introduction of long-acting injectables of any drug took 9 to 10 years after approval of its oral formulation. Mainly the market has been conquered by long-acting injectables for antipsychotic, substance abuse, and hormonal therapy drugs. This article focuses on the preparation of long-acting injectables with special emphasis on challenges associated with formulation. The evolution and current global market trend of various depot formulations are also discussed. Insight is provided into the promising future of long-acting injectables of protein-based drugs as well as multidrug therapy, along with potential uses in the treatment of chronic diseases like HIV, Parkinson's, and Alzheimer's.

在治疗许多慢性和危及生命的疾病时,由于患者的依从性更好,肠外给药途径优于口服给药途径。长效注射/贮存给药系统是用于在几天到几个月的长时间内延长/持续药物释放的制剂。仓库交付系统通过减少给药频率提高产品质量,简化药物治疗方案。肠外储存库降低疾病复发率和治疗维持期,从而提高疗效和治疗依从性。然而,尽管在过去的七十年中进行了广泛的探索,但只有少数仓库产品已上市或已达到商业可行性。任何药物的长效注射剂在其口服配方获得批准后都需要9到10年的时间。市场主要被抗精神病药物、药物滥用和激素治疗药物的长效注射剂所征服。本文重点介绍了长效注射剂的制备,特别强调了与配方相关的挑战。还讨论了各种仓库配方的演变和当前全球市场趋势。这项研究为蛋白质类药物的长效注射剂、多药治疗以及艾滋病、帕金森和阿尔茨海默病等慢性疾病的治疗提供了前景。
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引用次数: 36
Intranasal Delivery of Nanotherapeutics/ Nanobiotherapeutics for the Treatment of Alzheimer's Disease: A Proficient Approach. 鼻内给药纳米疗法/纳米生物疗法治疗阿尔茨海默病:一种熟练的方法。
IF 2.7 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2018026762
Namdev L Dhas, Ritu R Kudarha, Tejal A Mehta

Therapeutics and biotherapeutics-based fabrication of nanoparticles has fascinated scientists since the past two decades and exciting challenges have been surmounted. Particular interest has been paid to the exploitation of functionalized nanocarriers in the treatment of Alzheimer's disease (AD) using nasal route. Development of various material-based nanocarriers is a common approach to obtain advanced drug delivery systems possessing the ability to follow intranasal (IN) route for brain targeting, which would ultimately ameliorate the effect of AD. This review highlights the various pathological theories for AD along with their controversies. This work intends to provide a thorough, up-to-date, and holistic discussion on various pathways for nose-to-brain delivery and different formulation factors impacting on nasal absorption. The various material properties and their engineered nanocarriers as a smart delivery system, including synergistic effect of therapeutic/biotherapeutic agent in IN delivery as well as in AD therapy have been discussed. This review also emphasizes toxicity, especially neurotoxicity concerns pertaining to drug delivery systems.

在过去的二十年里,以治疗和生物治疗为基础的纳米颗粒制造一直吸引着科学家,并且已经克服了令人兴奋的挑战。特别感兴趣的是功能化纳米载体在阿尔茨海默病(AD)的鼻路治疗中的开发。开发各种基于材料的纳米载体是获得先进的药物递送系统的一种常见方法,该系统具有沿鼻内(IN)途径靶向大脑的能力,最终将改善AD的效果。本文综述了阿尔茨海默病的各种病理理论及其争议。这项工作旨在提供一个全面的,最新的,全面的讨论鼻到脑的各种途径和不同的配方因素影响鼻腔吸收。本文讨论了作为智能递送系统的各种材料特性及其工程纳米载体,包括治疗/生物治疗剂在in递送和AD治疗中的协同效应。本综述还强调毒性,特别是与药物传递系统有关的神经毒性。
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引用次数: 11
Nanoparticulate Carriers Used as Vaccine Adjuvant Delivery Systems. 纳米颗粒载体用作疫苗佐剂递送系统。
IF 2.7 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2019027047
Ning Wang, Rui Qian, Ting Liu, Tingni Wu, Ting Wang

Vaccination plays a crucial role in the control of infectious diseases, but often fails to eradicate certain refractory infections for which the development of an effective vaccine is eagerly desired but elusive. In many cases, failure in developing a vaccine is attributed to the inability of the candidates, especially among subunit vaccines, to evoke appropriate immuno-responses for establishing humoral as well as cellular immunity. In past decades, nanoparticles (NPs) sizing from 10 to 500 nm, such as liposomes, inorganic or metal NPs (iNPs), viruslike particles (VLPs), emulsions, immune-stimulating complexes (ISCOMs), and polymeric NPs, have been developed a potential carrier for vaccines to stabilize and deliver the adjuvant and antigens, thus forming proper vaccine adjuvant-delivery systems (VADSs). In particular, many NPs are rationally designed according to distinct cellular features and, therefore, are specifically engineered with functional materials so that they can deliver vaccine ingredients to target antigen-presenting cells (APCs) while directing immunoresponses against antigens along a specific Th1 (T helper type 1) and/or Th2 pathway to establish robust cellular and antibody immunity. In addition, a variety of NP-based VADSs are suitable for mucosal immunization, which contributes to systemic and, particularly, topical immunity, thus forming a dual barrier to pathogen invasion. This paper describes different NP-based VADSs designed for delivering vaccines, and evaluates their potential in the preparation of new products that can be used for prophylaxis against pathogens via different immunization routes.

疫苗接种在控制传染病方面起着至关重要的作用,但往往不能根除某些难治性感染,而开发有效的疫苗是迫切需要的,但却难以捉摸。在许多情况下,研制疫苗的失败是由于候选疫苗,特别是亚单位疫苗,无法唤起适当的免疫反应,以建立体液和细胞免疫。在过去的几十年里,粒径从10到500纳米的纳米颗粒(NPs),如脂质体、无机或金属纳米颗粒(iNPs)、病毒样颗粒(vlp)、乳剂、免疫刺激复合物(ISCOMs)和聚合物纳米颗粒(NPs),已被开发为疫苗的潜在载体,用于稳定和递送佐剂和抗原,从而形成适当的疫苗佐剂递送系统(vads)。特别是,许多NPs是根据不同的细胞特征合理设计的,因此,它们是用功能材料专门设计的,这样它们就可以将疫苗成分输送到靶向抗原呈递细胞(APCs),同时沿着特定的Th1 (T辅助型1)和/或Th2途径指导针对抗原的免疫反应,以建立强大的细胞和抗体免疫。此外,多种基于np的vads适合于粘膜免疫,有助于全身免疫,特别是局部免疫,从而形成对病原体入侵的双重屏障。本文描述了设计用于递送疫苗的不同的基于np的vads,并评估了它们在制备可通过不同免疫途径用于预防病原体的新产品方面的潜力。
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引用次数: 8
Polymeric Micelles for the Treatment of Rheumatoid Arthritis. 高分子胶束治疗类风湿关节炎。
IF 2.7 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-01-01 DOI: 10.1615/CRITREVTHERDRUGCARRIERSYST.2018021833
Linsen Yun, Hongtao Shang, Huan Gu, N. Zhang
Rheumatoid arthritis (RA) affects around 1% of the world's population and places heavy burdens on patients and society. RA pathogenesis has been studied for centuries, and findings suggest that it is activated by varied factors such as infection, genetic activation, and environmental changes, and travels differential pathways in patients, which increases the difficulty of treatment. There is currently no cure for RA. Current treatments inhibit inflammation, protect joints, and suppress immune cells like macrophages and T-lymphocytes. However, these therapies usually have issues of ineffectiveness, drug resistance, and many side effects. The reason is that therapies like methotrexate (MTX), dexamethasone (Dex), and cyclosporine A (CsA) are very lipophilic and have broad distribution in vivo. Micelles are ideal carriers to increase the solubility, bioavailability, half-life, and targeting of these hydrophobic drugs, and thus can be used for RA treatment. In the past decade, micelle-based therapies have become an attractive new strategy for RA treatment. This review summarizes the merits of micelles for RA, the therapeutic targets for RA, and studies that show the recent progress of developed micelles for RA. We compare the composition, performance, potential merits, and limitations of current therapies, and discusses the future directions of advanced and smart micelles for RA.
类风湿性关节炎(RA)影响着世界约1%的人口,给患者和社会带来沉重负担。几个世纪以来,人们对RA的发病机制进行了研究,研究结果表明,RA受感染、基因激活和环境变化等多种因素的激活,并在患者中传播不同的途径,这增加了治疗的难度。目前尚无治疗类风湿性关节炎的方法。目前的治疗方法可以抑制炎症,保护关节,抑制免疫细胞,如巨噬细胞和t淋巴细胞。然而,这些疗法通常有无效、耐药和许多副作用的问题。原因是甲氨蝶呤(MTX)、地塞米松(Dex)和环孢素A (CsA)等治疗具有非常亲脂性,并且在体内分布广泛。胶束是提高疏水药物的溶解度、生物利用度、半衰期和靶向性的理想载体,因此可用于类风湿性关节炎的治疗。在过去的十年中,基于胶束的治疗已经成为一种有吸引力的治疗RA的新策略。本文综述了胶束治疗RA的优点、RA的治疗靶点以及近年来胶束治疗RA的研究进展。我们比较了目前治疗方法的组成、性能、潜在优点和局限性,并讨论了先进和智能胶束治疗RA的未来方向。
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引用次数: 13
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