摘要
背景:由于药物分子的物理化学特性和生理效应的差异,寻找用于增强的临床前和临床药物递送以及细胞靶向的智能递送系统仍然是主要的生物医学研究尝试,并且这影响递送机制以引发最大的治疗效果。有针对性的药物输送是一种智能的进化,对于解决传统药物输送系统相关的主要挑战至关重要。由于活性药物成分不能特异性地作用于恶性细胞,导致较差的治疗指数和对周围正常细胞的毒性,这些挑战大多导致较差的药代动力学。适体是具有工程亲和力的寡核苷酸以特异性结合其同源靶标。适体作为有效的靶向元件获得了显着的兴趣,因为它们可以被生成为特异性结合到包括蛋白质,肽,离子,细胞和组织的广泛靶标。尽管如此,作为治疗载体的适体的有效递送受到细胞膜静电排斥,内切核酸酶降解,低pH切割和结合构象稳定性的挑战。 目标:分子工程生物可降解和生物相容性聚合物颗粒的应用,具有可调整的特征,如表面积和化学性质,颗粒大小分布和毒性,为开发智能适体介导的控释药物释放系统创造机会。 结果:本文讨论通过将活性成分通过细胞和生物分子交通导向靶位以持续和受控释放以有效治疗剂量同时使系统性细胞毒性效应最小化来促进微粒适体药物制剂推进当前药物递送模式的机会。 结论:提出了一种采用分阶段递送机制的适体 - 药物制剂的新型药物 - 聚合物 - 适体 - 聚合物(DPAP)设计方案,以说明适体 - 聚合物载体用于增强的细胞靶向和药物递送的潜在功效。
关键词: 适体,药物输送,生物可降解聚合物,包封,细胞靶向,DPAP。
Current Drug Targets
Title:Aptamer-Mediated Polymeric Vehicles for Enhanced Cell-Targeted Drug Delivery
Volume: 19 Issue: 3
关键词: 适体,药物输送,生物可降解聚合物,包封,细胞靶向,DPAP。
摘要: Background: The search for smart delivery systems for enhanced pre-clinical and clinical pharmaceutical delivery and cell targeting continues to be a major biomedical research endeavor owing to differences in the physicochemical characteristics and physiological effects of drug molecules, and this affects the delivery mechanisms to elicit maximum therapeutic effects. Targeted drug delivery is a smart evolution essential to address major challenges associated with conventional drug delivery systems. These challenges mostly result in poor pharmacokinetics due to the inability of the active pharmaceutical ingredients to specifically act on malignant cells thus, causing poor therapeutic index and toxicity to surrounding normal cells. Aptamers are oligonucleotides with engineered affinities to bind specifically to their cognate targets. Aptamers have gained significant interests as effective targeting elements for enhanced therapeutic delivery as they can be generated to specifically bind to wide range of targets including proteins, peptides, ions, cells and tissues. Notwithstanding, effective delivery of aptamers as therapeutic vehicles is challenged by cell membrane electrostatic repulsion, endonuclease degradation, low pH cleavage, and binding conformation stability.
Objective: The application of molecularly engineered biodegradable and biocompatible polymeric particles with tunable features such as surface area and chemistry, particulate size distribution and toxicity creates opportunities to develop smart aptamer-mediated delivery systems for controlled drug release.
Results: This article discusses opportunities for particulate aptamer-drug formulations to advance current drug delivery modalities by navigating active ingredients through cellular and biomolecular traffic to target sites for sustained and controlled release at effective therapeutic dosages while minimizing systemic cytotoxic effects.
Conclusion: A proposal for a novel drug-polymer-aptamer-polymer (DPAP) design of aptamer-drug formulation with stage-wise delivery mechanism is presented to illustrate the potential efficacy of aptamer- polymer cargos for enhanced cell targeting and drug delivery.
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Cite this article as:
Aptamer-Mediated Polymeric Vehicles for Enhanced Cell-Targeted Drug Delivery, Current Drug Targets 2018; 19 (3) . https://dx.doi.org/10.2174/1389450117666160617120926
DOI https://dx.doi.org/10.2174/1389450117666160617120926 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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