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Theranostic Nanostructures for Ovarian Cancer. 纳米结构治疗卵巢癌。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2019-01-01 DOI: 10.1615/CRITREVTHERDRUGCARRIERSYST.2018025589
B. Navyatha, S. Nara
Ovarian cancer (OC) has emerged as one of the leading causes of death in women due to the lack of early-stage diagnosis resulting in impairment and delay in treatment of malignancy, which raises the morality rate. Existing diagnostic (pelvic examination, CA125, and enzyme-linked immunosorbent assay) or therapeutic modalities (radiotherapy, abdominal pelvic radiation therapy, and chemotherapy) are insufficient to decrease the 5-year survival rate. Nanoparticles (NPs) have been extensively explored as probes for imaging or therapy of cancer. As an extension of this, probes have been designed to possess both imaging and therapeutic modality in a single molecule and this has emerged as the science of nanotheranostics. This review presents the existing diagnostic and therapeutic strategies in use for OC and discusses their loopholes that limit the prognosis of OC. The review presents a general description of important properties of nanostructures and the type of nanostructures that have been used as imaging/therapeutic probe in cancer. The state-of-the-art nanotheranostics probe for targeting OC is presented. Systematic and complete studies that can correlate the findings of researchers from different global areas are lacking. The current status of nanostructures in various phases of clinical trials and those approved by U.S. Food and Drug Administration (FDA) has been presented. No specific targeted theranostic probe for OC has yet been approved by the FDA. Here, the underlying reasons and the challenges faced for nanotheranostics of OC are discussed, along with its future prospects.
卵巢癌已成为妇女死亡的主要原因之一,原因是缺乏早期诊断,导致恶性肿瘤的损害和治疗延误,从而提高了死亡率。现有的诊断(盆腔检查、CA125和酶联免疫吸附试验)或治疗方式(放疗、腹腔盆腔放疗和化疗)不足以降低5年生存率。纳米颗粒(NPs)作为肿瘤成像或治疗的探针已被广泛探索。作为这方面的延伸,探针被设计成在单个分子中同时具有成像和治疗模式,这已经成为纳米治疗科学。本文综述了目前用于卵巢癌的诊断和治疗策略,并讨论了其限制卵巢癌预后的漏洞。本文综述了纳米结构的重要特性和纳米结构的类型,这些纳米结构已被用作癌症的成像/治疗探针。提出了针对OC的最先进的纳米治疗探针。缺乏能够将全球不同地区的研究人员的发现联系起来的系统和完整的研究。介绍了纳米结构在临床试验的各个阶段和美国食品和药物管理局(FDA)批准的纳米结构的现状。目前还没有针对OC的特异性靶向治疗探针得到FDA的批准。本文讨论了纳米肿瘤治疗的潜在原因和面临的挑战,并展望了其未来前景。
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引用次数: 2
Pancreatic Cancer: Recent Advances in Nanoformulation-Based Therapies. 胰腺癌:基于纳米制剂疗法的最新进展。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2019-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2018025459
Preshita Desai, David Ann, Jeffrey Wang, Sunil Prabhu

Pancreatic cancer is the fourth leading cause of death in the United States and has a 5-year life expectancy of ~8%. Currently, only a few drugs have been approved by the United States Food and Drug Administration for pancreatic cancer treatment. Despite available drug therapy and ongoing clinical investigations, the high prevalence and mortality associated with pancreatic cancer mean that there is an unmet chemopreventive and therapeutic need. From ongoing studies with various novel formulations, it is evident that the development of smart drug delivery systems will improve delivery of drug cargo to the pancreatic target site to ensure and enhance the therapeutic/chemoprevention efficacy of existing drugs and newly designed drugs in the future. With this in view, nanotechnology is emerging as a promising avenue to enhance drug delivery to the pancreas via both passive and active targeting mechanisms. Research in this field has grown extensively over the past decade, as is evident from available scientific literature. This review summarizes the recent advances that have brought nanotechnology-based formulations to the forefront of pancreatic cancer treatment.

胰腺癌是美国第四大死因,5 年预期寿命约为 8%。目前,美国食品和药物管理局只批准了几种治疗胰腺癌的药物。尽管有药物治疗和正在进行的临床研究,但与胰腺癌相关的高发病率和死亡率意味着化学预防和治疗需求尚未得到满足。从目前对各种新型制剂的研究中可以看出,智能给药系统的开发将改善药物向胰腺靶点的输送,从而确保并提高现有药物和未来新设计药物的治疗/化学预防功效。有鉴于此,纳米技术正成为通过被动和主动靶向机制加强胰腺药物输送的一条大有可为的途径。从现有的科学文献中可以看出,该领域的研究在过去十年中得到了广泛的发展。本综述总结了将基于纳米技术的制剂推向胰腺癌治疗前沿的最新进展。
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引用次数: 0
Solid Lipid Nanoparticles: Vital Characteristics and Prospective Applications in Cancer Treatment. 固体脂质纳米颗粒:在癌症治疗中的重要特性和前景应用。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2019-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2019020396
Leontin F Lazăr, Elena Diana Olteanu, Radu Iuga, Claudia Burz, Marcela Achim, Simona Clichici, Lucia R Tefas, Iuliana Nenu, Diana Tudor, Ioana Baldea, Gabriela Adriana Filip

Cancer nanotechnology is a new field of interdisciplinary research cutting across biology, chemistry, engineering, and medicine, aiming to lead to major advances in cancer treatment. Over the past several years, solid lipid nanoparticles (SLNs) have attracted the interest of researchers due to their ability to overcome the limitations of classic chemotherapeutics. We reviewed the most recent data on the therapeutic use of SLNs in oncology, presenting their main advantages and disadvantages, along with various production methods and different routes of administration. In accordance with these aspects, the long-term physical stability, the controlled release of the loaded drugs, and the efficient targeted delivery of drugs as methods of surpassing the pharmaceutical limitations of anticancer drugs, natural products and gene therapy have been discussed. In addition, we have also emphasized briefly the crosstalk between SLNs and the new trend in oncology, immunotherapy, as future possible antineoplastic treatment, especially in melanoma. This review highlights the potential of SLNs in providing very positive perspectives for future cancer treatment by improving the efficiency of present chemotherapy and reducing its side effects. SLNs allow targeted delivery of anticancer drugs and could improve the efficiency of current chemotherapy in neoplasia.

癌症纳米技术是一个跨学科研究的新领域,跨越了生物学、化学、工程学和医学,旨在导致癌症治疗的重大进展。在过去的几年中,固体脂质纳米颗粒(sln)因其克服传统化疗药物局限性的能力而引起了研究人员的兴趣。我们回顾了sln在肿瘤治疗中的最新数据,介绍了它们的主要优点和缺点,以及各种生产方法和不同的给药途径。针对这些方面,探讨了药物的长期物理稳定性、载药的控释以及药物的高效靶向递送作为超越抗癌药物、天然产物和基因治疗药物局限性的方法。此外,我们还简要地强调了sln与肿瘤学、免疫治疗的新趋势之间的相互作用,作为未来可能的抗肿瘤治疗,特别是黑色素瘤治疗。这篇综述强调了sln的潜力,通过提高目前化疗的效率和减少其副作用,为未来的癌症治疗提供了非常积极的前景。sln允许靶向递送抗癌药物,并可以提高当前肿瘤化疗的效率。
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引用次数: 6
Inhalational Drug Delivery in Pulmonary Aspergillosis. 肺曲霉病的吸入给药。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2019-01-01 DOI: 10.1615/CRITREVTHERDRUGCARRIERSYST.2018025781
Ranjot Kaur, R. Kaur, C. Singh, Shahdeep Kaur, A. Goyal, K. Singh, Bhupinder Singh
Pulmonary infections have long represented one of the major threats to humans. These vary from acute to chronic conditions, depending upon the underlying disease of the airways. Pulmonary aspergillosis (PMAP) has raised vital concerns in the immunocompromised patients. The fungal infection is difficult to diagnose in the early stages, often making the disease more complicated. Currently, three classes of antifungal agents are available on the market for the treatment of pulmonary infections. These agents are available in oral and intravenous forms only, which limits the availability of therapeutic concentrations of drug in the lungs for longer durations. Consequently, this leads to therapeutic failure and/or resistance of the organism(s) towards the antifungal agents because the optimum amount of drug does not reach the infection site. To combat the issues associated with the conventional regimens, inhalation of antifungal agents is gaining importance because administration to the lungs offers huge advantages of localized and targeted delivery. A wide range of inhalational devices such as nebulizers, dry powder inhalers, and metered dose inhalers are available on the market to deliver drug molecules to the lungs effectively. However, their clinical utility is limited to conditions such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis only. For a few decades, inhalation therapy has also been gaining importance to treat infectious diseases such as tuberculosis and aspergillosis, though more research efforts are required to make the transition from bench to bedside. The current review provides an explicit account of the potential role of inhalation drug delivery in PMAP.
长期以来,肺部感染一直是人类面临的主要威胁之一。根据气道的潜在疾病,这些情况从急性到慢性各不相同。肺曲霉病(PMAP)引起了免疫功能低下患者的严重关注。真菌感染在早期阶段很难诊断,往往使疾病更加复杂。目前,市场上有三种抗真菌药物可用于治疗肺部感染。这些药物仅以口服和静脉注射形式提供,这限制了治疗浓度药物在肺部较长时间的可用性。因此,这会导致治疗失败和/或生物体对抗真菌药物产生耐药性,因为最佳剂量的药物没有到达感染部位。为了解决与传统治疗方案相关的问题,吸入抗真菌药物变得越来越重要,因为给药到肺部提供了局部和靶向递送的巨大优势。市场上有各种吸入装置,如雾化器、干粉吸入器和计量吸入器,可将药物分子有效地输送到肺部。然而,它们的临床应用仅限于哮喘、慢性阻塞性肺疾病和囊性纤维化等疾病。几十年来,吸入疗法在治疗肺结核和曲霉病等传染病方面也越来越重要,尽管需要更多的研究努力才能从实验室过渡到临床。目前的综述提供了吸入给药在PMAP中的潜在作用的明确说明。
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引用次数: 9
Current Developments in Therapeutic Drug Targeting for the Management of Rheumatoid Arthritis: An Emerging Paradigm. 类风湿性关节炎治疗药物靶向治疗的最新进展:一个新兴的范例。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2019-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2019025729
Deeksha R Pai, Madhugiri Prakash Venkatesh, T M Pramod Kumar

Rheumatoid arthritis (RA) is a debilitating condition that results in impairment of joints and ligaments and thus constrained mobility and decreased array of movement. It is a broad expression that encompasses additional 100 very diverse disorders mainly affecting joints. In the field of drug discovery, there is no well-known treatment for RA that can eradicate the disease permanently and alleviate the pain. The common non-targeted treatment approaches leads to serious side effects and systemic complications for RA patients. Therefore, targeted drug delivery systems, strategies, and diverse therapeutic approach for treatment of RA have gained increasing attention in the past few years. However, with the current understandings, researchers aim at accomplishing complete and long-lasting remission by the development of smart formulations/smart drug-delivery systems. Treatment for RA patients can be more efficient and effective utilizing these smart approaches. The present review focuses on the existing novel drug-delivery systems, strategies, and current trends in the treatment of RA.

类风湿性关节炎(RA)是一种使人衰弱的疾病,导致关节和韧带损伤,从而限制活动能力和减少运动。它是一个广泛的表达,包括另外100种主要影响关节的非常不同的疾病。在药物发现领域,目前还没有一种众所周知的治疗类风湿性关节炎的方法可以永久根除这种疾病并减轻疼痛。常见的非靶向治疗方法导致RA患者严重的副作用和全身性并发症。因此,靶向给药系统、策略和治疗RA的多种治疗方法在过去几年中得到了越来越多的关注。然而,根据目前的理解,研究人员的目标是通过开发智能配方/智能给药系统来实现完全和持久的缓解。利用这些智能方法,对RA患者的治疗可以更有效。目前的综述集中在现有的新的药物传递系统,策略和目前的趋势治疗类风湿性关节炎。
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引用次数: 3
Dendrimers for Therapeutic Delivery: Compositions, Characterizations, and Current Status. 用于治疗递送的树状大分子:组成、特征和现状。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2019-01-01 DOI: 10.1615/CRITREVTHERDRUGCARRIERSYST.2018025749
K. Nagpal, Pradeep Kumar, A. Mohan, Sourav Thakur
Dendrimers, commonly referred to as arborols, offer tremendous opportunities for drug delivery, diagnostics, and treatment applications. This may be attributed to the characteristic features of their three architectural components: core, branches, and terminal groups. These components provide vast flexibility to designers. They act as highly moldable platforms that can be modified to suit the needs of application designers. Effectively, the type, length, and molecular weight of the core, branches and terminal groups may be customized to achieve desired characteristics and satisfy the demands of numerous applications. These perfectly designed multifunctional structures are reviewed in the current paper, focusing on their complex archetypical design for interphase applications; novel drug delivery applications, especially oral, ocular, pulmonary, transdermal; targeted, and controlled-release; and diagnosis and treatment of diseases like cancer, diabetes, and autoimmune disorders.
树状大分子,通常被称为树酚,为药物输送、诊断和治疗应用提供了巨大的机会。这可能归因于它们的三个体系结构组件的特征:核心、分支和终端组。这些组件为设计人员提供了极大的灵活性。它们充当高度可建模的平台,可以根据应用程序设计人员的需要进行修改。实际上,可以定制核心、分支和端基的类型、长度和分子量,以达到所需的特性,满足众多应用的需求。本文综述了这些完美设计的多功能结构,重点介绍了它们在间相应用中的复杂原型设计;新型给药应用,特别是口服、眼、肺、透皮;定向控释;以及癌症、糖尿病和自身免疫性疾病等疾病的诊断和治疗。
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引用次数: 7
Evaluation of Nanocarrier-Based Dry Powder Formulations for Inhalation with Special Reference to Anti-Tuberculosis Drugs. 纳米载体干粉吸入制剂的评价,特别是抗结核药物。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2019-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2018024397
T. Patil, A. Deshpande, P. Shende, Shirish Deshpande, R. Gaud
Pulmonary tuberculosis (TB) is a leading cause of death worldwide and is caused by the pathogen Mycobacterium tuberculosis (MTb). As treatment for TB, dry powders for inhalation (DPIs) are considered stable compared with nebulizers and metered dose inhalers and are suitable for high-dose formulations. Although extensive research has been done over the last two to three decades on nanocarrier-based DPIs for targeting MTb infection, none of the anti-TB DPI formulations have reached the market. Challenges in the proper assessment of nanocarrier-based DPIs due to the complexity of lungs is one of the reasons. In this review, the details of in vitro evaluation parameters of nanocarriers and nanocarrier-based DPIs along with their need and basic principles are discussed. Further, the thorough in vitro, ex vivo, and in vivo pharmacological evaluations, together with their procedures wherever required, are covered. The different evaluation parameters during process development, release specifications, and stability studies suggested by U.S. Food and Drug Administration Center for Drug Evaluation and Research to apply for new drug applications and abbreviated new drug applications of DPIs are also discussed. Lastly, the evaluation parameters for DPIs provided in European, United States, British, and Indian pharmacopeias are summarized.
肺结核(TB)是世界范围内死亡的主要原因,由结核分枝杆菌(MTb)引起。作为结核病的治疗方法,与雾化器和计量吸入器相比,吸入干粉被认为是稳定的,适用于高剂量制剂。尽管在过去的二三十年中对靶向结核分枝杆菌感染的基于纳米载体的DPI进行了广泛的研究,但没有一种抗结核DPI制剂进入市场。其中一个原因是由于肺部的复杂性,在正确评估基于纳米载体的dpi方面存在挑战。本文综述了纳米载体及基于纳米载体的dpi体外评价参数的研究现状、必要性和基本原理。此外,全面的体外,离体和体内药理学评估,连同他们的程序,无论需要,都包括在内。讨论了美国食品药品监督管理局药物评价与研究中心在dpi新药申请和简略新药申请中建议的不同工艺开发评价参数、释放规范和稳定性研究。最后,对欧洲、美国、英国和印度药典中dpi的评价参数进行了总结。
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引用次数: 5
In Situ Forming Depot as Sustained-Release Drug Delivery Systems. 原位成形库作为缓释给药系统。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2019-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2018025013
Navjot Kanwar, Vivek Ranjan Sinha

In situ forming systems can serve as promising alternative to existing long acting injectables like disperse systems and microspheres, owing to their biocompatibility, stability, ease of administration and scale up. Microspheres based on long-acting parenteral systems pose challenges in scaling up and process changes with the drug and polymer selected. In situ gelling systems are having low viscosity which is very conducive during various manufacturing unit operations and passing the formulation through hypodermic needle with lower applied pressure. Different mechanisms such as physical or physiological stimuli and cross linking reactions are involved in the gelling of in situ forming systems at the site of injection. Drug release from in situ forming systems can be altered according to the need by using different polymers, lipids and fatty acids. In situ forming systems can be evaluated by sol-gel transition time, temperature and pH, rheology, gel strength, texture analysis, syringeability and injectability. The present paper is an overview of the various in situ gelling polymers and their application in the preparation of depot formulations. Numerous products based on in situ forming systems such as Eligard®, Atridox® are available in market.

由于原位成型系统具有生物相容性、稳定性、易于管理和规模化,因此可以作为现有长效注射剂(如分散系统和微球)的有希望的替代品。基于长效肠外系统的微球在扩大规模和随着药物和聚合物的选择而改变工艺方面提出了挑战。原位胶凝系统具有低粘度,这在各种制造单元操作中非常有利,并且以较低的施加压力将配方通过皮下注射针。不同的机制,如物理或生理刺激和交联反应参与了原位成形系统在注射部位的胶凝。原位成形系统的药物释放可以根据需要通过使用不同的聚合物、脂类和脂肪酸来改变。可以通过溶胶-凝胶转变时间、温度和pH、流变性、凝胶强度、结构分析、注射性和注射性来评价原位成型体系。本文综述了各种原位胶凝聚合物及其在仓库配方制备中的应用。市场上有许多基于现场成形系统的产品,如Eligard®,Atridox®。
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引用次数: 27
Polymeric Mixed Micelles: Improving the Anticancer Efficacy of Single-Copolymer Micelles. 聚合物混合胶束:提高单共聚胶束的抗癌效果。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2019-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2018020481
Arehalli S Manjappa, Popat S Kumbhar, John I Disouza, Vandana B Patravale

Mixed micelles self-assembled from two or more dissimilar block copolymers provide a direct and convenient approach to improved drug delivery. The present review is focused on mixed micelles (prepared from block copolymers only) for various drug delivery applications along with their merits over single-copolymer micelles. Presented are the physicochemical properties of mixed and single-copolymer micelles, various stimuli-responsive mixed micelles for the treatment of cancer, interesting combinations of multifunctional mixed micelles along with their in vitro and in vivo performance, and the potential of mixed micelles as a gene delivery system. Finally, the performance of mixed micelles in preclinical and clinical testing is explained. In addition, the interaction of mixed micelles with cancer cells and the biosafety of mixed micelles are summarized. The in vitro and in vivo performance presented here clearly reveals that the mixed-micelle approach has a wider scope than that of the single-copolymer micelle approach and directs researchers to focus on this approach to delivery of drugs/gene/biologics for various applications.

由两种或多种不同嵌段共聚物自组装的混合胶束为改善药物传递提供了直接和方便的方法。目前的综述集中在混合胶束(仅由嵌段共聚物制备)用于各种药物输送应用以及它们比单共聚物胶束的优点。介绍了混合胶束和单共聚物胶束的物理化学性质,用于治疗癌症的各种刺激响应混合胶束,多功能混合胶束的有趣组合及其体外和体内性能,以及混合胶束作为基因传递系统的潜力。最后,阐述了混合胶束在临床前和临床试验中的性能。此外,还综述了混合胶束与癌细胞的相互作用以及混合胶束的生物安全性。这里展示的体外和体内性能清楚地揭示了混合胶束方法比单共聚物胶束方法具有更广泛的应用范围,并指导研究人员将重点放在这种方法上,以用于各种应用的药物/基因/生物制剂的递送。
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引用次数: 28
Current Perspectives on Novel Drug Carrier Systems and Therapies for Management of Pancreatic Cancer: An Updated Inclusive Review. 胰腺癌治疗的新型药物载体系统和治疗方法的最新进展:一项最新的包容性综述。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2018-01-01 DOI: 10.1615/CritRevTherDrugCarrierSyst.2018019429
Rohit Rajendra Bhosale, Hosahalli Veerabhadrappa Gangadharappa, Devegowda Vishakante Gowda, Riyaz Ali Mahafez Ali Osmani, Rudra Vaghela, Parthasarathi Keshavarao Kulkarni, Koganti Venkata Sairam, Bannimath Gurupadayya

Pancreatic cancer (PC) is one of the most fatal solid tumors, resulting in more than 250,000 deaths per year globally. It is the eighth leading cause of death from cancer in men and women throughout the world and is now third leading cause of cancer-related deaths in the United States. In addition, the worldwide occurrence of PC ranges from 1 to 10 cases per 100,000 people, indicating a higher incidence in developed countries. Most patients with locally advanced or metastatic disease are not candidates for curative resection due to enormously poor prognosis. Substantial efforts have been taken during the past decade to distinguish better treatments in the absence of efficient screening methods. Regardless of wide-ranging efforts, various systems and therapies have shown insufficient efficacy for PC patients. Therefore, the development of novel drug delivery systems, strategies, and diverse therapeutic approaches to improve the range of active molecules for the treatment of PC is critical. Currently, cancer research focuses on improving the treatment of PC via diverse novel drug delivery systems of chemotherapeutic agents. These novel drug delivery systems consist of nanoparticles and liposomes. Strategies or therapeutic approaches intended for PC include radiation therapy, ablation therapy, and gene therapy. These systems and approaches can carry the drug molecules to targeted cancer cells to enhance the effectiveness of tumor penetration. The present review encloses existing novel drug carrier systems and approaches for PC management.

胰腺癌(PC)是最致命的实体肿瘤之一,每年导致全球超过25万人死亡。它是全世界男性和女性癌症死亡的第八大原因,现在是美国癌症相关死亡的第三大原因。此外,全世界PC的发病率为每10万人中有1至10例,表明发达国家的发病率更高。由于预后极差,大多数局部晚期或转移性疾病的患者不适合进行根治性切除。在过去十年中,在缺乏有效筛查方法的情况下,已经作出了大量努力来区分更好的治疗方法。尽管进行了广泛的努力,但各种系统和疗法对PC患者的疗效不足。因此,开发新的药物传递系统、策略和多样化的治疗方法来提高治疗PC的活性分子的范围是至关重要的。目前,癌症研究的重点是通过多种化疗药物的新型药物传递系统来改善PC的治疗。这些新型给药系统由纳米颗粒和脂质体组成。针对PC的策略或治疗方法包括放射治疗、消融治疗和基因治疗。这些系统和方法可以携带药物分子到靶向癌细胞,以提高肿瘤穿透的有效性。本文综述了现有的新型药物载体系统和PC管理方法。
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引用次数: 10
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