Nanotechnology-Based Drug Delivery Systems for Targeting, Imaging and Diagnosis of Neurodegenerative Diseases

Neurodegenerative disorders are becoming prevalent with the increasing age of the general population. A number of difficulties have emerged for the potential treatment of neurodegenerative diseases, as these disorders may be multi systemic in nature. Due to limitations regarding the blood brain barrier (BBB) structure, efflux pumps and metabolic enzyme expression, conventional drug delivery systems do not provide efficient therapy for neurodegenerative disorders. Nanotechnology can offer impressive improvement of the neurodegenerative disease treatment by using bio-engineered systems interacting with biological systems at a molecular level. This review focuses on the nano-enabled system applications for the treatment and diagnosis of neurodegenerative diseases, in particular Alzheimer’s, Parkinson’s and Prion diseases.     

Designing Dendrimers for Drug Delivery and Imaging: Pharmacokinetic Considerations

Dendrimers have well-organized high branches with a layered architecture providing a series of versatile chemical modification for various purposes. Consequently, this dendrimer nanotechnology explores a new promising class of nanoscale carriers for therapeutic drugs and imaging reagents using passive and active targeting approaches. By controlling dendritic structures, the biological fate of dendrimer/dendrimer-based drugs can be significantly altered based on their intrinsic physicochemical properties, including the hydrophilicity of the unit molecules, particle size, surface charge, and modification. Accordingly, pharmacokinetic aspects play an important role in the design and development of dendrimer systems for successful in vivo application and clinical translation. This review focuses on the recent progress regarding dendritic architectures, structure-related toxicity, and critical factors affecting the pharmacokinetics and biodistribution of dendrimer/dendrimer-based drugs. A better understanding of the basic aspects of dendritic systems and their pharmacokinetics will help to develop a rationale for the design of dendrimers for the controlled delivery of drugs and imaging reagents for therapeutic or diagnostic purposes.     

Imaging the Cytosolic Drug Delivery Mechanism of HDL-Like Nanoparticles

Purpose

Molecular therapeutics often require an effective nanoparticle-based delivery strategy to transport them to cytosolic organelles to be functional. Recently, a cytosolic delivery strategy based on the scavenger receptor class B type I (SR-BI) mediated pathway has shown great potential for the effective delivery of theranostics agents into the cytoplasm of cells without detrimental endosomal entrapment. This study elucidates this unique delivery mechanism for improving cytosolic drug delivery.

Methods

Multifluorophore-labeled HDL-mimicking peptide phospholipid scaffold (HPPS) nanoparticles were developed. Fluorescence imaging was utilized to examine HPPS transporting payloads into cells step by step through sequential inhibition studies.

Results

HPPS specifically recognizes and binds to SR-BI, then interacts with SR-BI, which results in direct transport of payload molecules into the cell cytoplasm without entire particles internalization. The cytosolic transport of payloads occurred through a temperature- and energy-independent pathway, and was also different from actin- and clathrin-mediated endocytosis. Furthermore, this transport was significantly inhibited by disruption of lipid rafts using filipin or methyl-β-cyclodextrin.

Conclusions

The cytosolic delivery of payloads by HPPS via SR-BI targeting is predominately mediated through a lipid rafts/caveolae-like pathway. This cytosolic delivery strategy can be utilized for transporting molecular therapeutics that require their action sites to be within cytosolic organelles to enhance therapeutic effect.     

PEG-Functionalized Magnetic Nanoparticles for Drug Delivery and Magnetic Resonance Imaging Applications

Purpose  

Polyethylene glycol (PEG) functionalized magnetic nanoparticles (MNPs) were tested as a drug carrier system, as a magnetic resonance imaging (MRI) agent, and for their ability to conjugate to an antibody.     

Nanoparticle-Mediated Cytoplasmic Delivery of Messenger RNA Vaccines: Challenges and Future Perspectives

Pharmaceutical Research - The COVID-19 pandemic has left scientists and clinicians no choice but a race to find solutions to save lives while controlling the rapid spreading. Messenger RNA...     

Improved Delivery Through Biological Membranes. XXIV. Synthesis,in Vitro Studies,and in Vivo Characterization of Brain-Specific and Sustained Progestin Delivery Systems

Dihydropyridine pyridinium salt-based brain-selective delivery systems were synthesized for the progestins, ethisterone, norethindrone, and norgestrel. After initial lipophilicity and in vitro studies indicated the feasibility of applying these compounds to brain-specific delivery, in vivo distribution studies were performed on one of the redox delivery systems. After systemic administration of the chemical delivery system based on norethindrone, sustained and selective delivery of the oxidized form of the drug–carrier complex was observed in the brain. In addition, a slow and sustained release of the parent steroid, norethindrone, occurred. This release produced substantially higher levels of norethindrone for more prolonged periods than the administration of norethindrone itself.     

Imaging of Cells and Nanoparticles: Implications for Drug Delivery to the Brain

A major challenge in the development of central nervous system drugs is to obtain therapeutic effective drug concentrations inside the brain. Many potentially effective drugs have never reached clinical application because of poor brain penetration. Currently, devices are being developed that may improve drug delivery into the brain. One approach involves the encapsulation of drugs into nanocarriers that are targeted to the brain, where the drug is released. Alternatively, living cells have been engineered to produce the pharmaceutical of interest at the target site. It is important to follow the fate of these drug delivery devices inside the body to verify their efficiency in reaching the brain. To this end, both ex-vivo approaches and in-vivo imaging techniques are used, including ex-vivo biodistribution, autoradiography, MRI, optical imaging, PET and SPECT. All these methods have their specific advantages and limitations. Consequently, selection of the tracking method should be based on the specific aims of the experiment. Here, we will discuss the methods that are currently applied for tracking brain drug delivery devices, including the most commonly used labels and labeling procedures for living cells and nanocarriers. Subsequently, we will discuss specific applications in tracking drug delivery devices.     

纳米晶递药体系在肿瘤诊疗领域研究进展

纳米晶材料因其独特的尺寸和优异的理化性能近年来备受关注,基于纳米晶理论和实践的研究,显示了其广阔的生物医学应用前景。重点简介纳米晶的定义、分类、制备及修饰工艺,综述多种纳米晶体系在肿瘤诊疗及临床应用中的研究进展,分析讨论纳米晶在生物应用时的体内过程和存在的技术问题,为基于纳米晶的递送体系在肿瘤诊疗领域进一步开发提供参考。     

利用小动物活体成像技术快速评价呼吸道给药效果

目的:通过小动物活体成像观察荧光物质在动物呼吸道的分布,以快速评价呼吸道给药效果。方法:昆明种小鼠鼻腔吸入给予Cy5.5荧光标记的脂质基因复合物气雾剂设为实验组,同时设立阳性对照组,采用气道插管方式注入与实验组等量复合物无水乙醚溶液,阴性对照组吸入给予等量不含Cy5.5标记的气雾剂,观察气雾颗粒在各组小鼠呼吸道的荧光分布。结果:与阴性对照组比较,实验组和阳性对照组小鼠的呼吸道内均有强烈的荧光显示。结论:小动物活体成像技术可能成为呼吸道给药效果的快速、有效的评价方法。     

Transfollicular Drug Delivery

The hair follicle, hair shaft, and sebaceous gland collectively form what is recognized as the pilosebaceous unit. This complex, three-dimensional structure within the skin possesses a unique biochemistry, metabolism and immunology. Recent studies have focused on the hair follicle as a potential pathway for both localized and systemic drug delivery. Greater understanding of the structure and function of the hair follicle may facilitate rational design of drug formulations to target follicular delivery. Targeted drug delivery may enhance current therapeutic approaches to treating diseases of follicular origin. Presented here is a review of follicular drug delivery and a discussion of the feasibility of the pilosebaceous unit as a target site.     

Ocular Drug Delivery

Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood–retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.     

Brain-Targeted Drug Delivery

Because the brain is tightly segregated from the circulating blood by a unique membranous barrier, the blood-brain barrier (BBB), many pharmaceuticals cannot be efficiently delivered to, or sustained within the brain; hence, they are ineffective in treating cerebral diseases. Therefore, drug delivery methods that can provide brain delivery, or eventually preferential brain delivery (i.e. brain targeting), are of particular interest. To achieve successful delivery, an understanding of the major structural, enzymatic, and active transport aspects related to the BBB, and of the issues related to lipophilicity and its role in CNS entry, is critical. During the last years, considerable effort was focused in the field of brain-targeted drug delivery. Various more or less sophisticated approaches, such as intracerebral delivery, intracerebroventricular delivery, intranasal delivery, BBB disruption, nanoparticles, receptor mediated transport (vector-mediated transport or ‘chimeric’ peptides), cell-penetrating peptides, prodrugs, and chemical delivery systems, have been attempted. These approaches may offer many intriguing possibilities for brain delivery and targeting, but only some have reached the phase where they can provide safe and effective human applications. Site-target indexing and the use of targeting enhancement factors can be used to quantitatively assess the site-targeting effectiveness from a pharmacokinetic perspective of chemical delivery systems.     

In Drug Delivery,Shape Does Matter

Pharmaceutical Research -     

In Drug Delivery,Shape Does Matter

Pharmaceutical Research -     

药物传递途径及相关技术

发展安全高效 药物传递途径和技术是促进药物临床应用的关键。该文从药物科学技术的角度提供一个视野来呈现药和传递途径及相关技术的最近发展和新思维,并对此进行简单扼要的专业评述。     

Polymer Architecture and Drug Delivery

Polymers occupy a major portion of materials used for controlled release formulations and drug-targeting systems because this class of materials presents seemingly endless diversity in topology and chemistry. This is a crucial advantage over other classes of materials to meet the ever-increasing requirements of new designs of drug delivery formulations. The polymer architecture (topology) describes the shape of a single polymer molecule. Every natural, seminatural, and synthetic polymer falls into one of categorized architectures: linear, graft, branched, cross-linked, block, star-shaped, and dendron/dendrimer topology. Although this topic spans a truly broad area in polymer science, this review introduces polymer architectures along with brief synthetic approaches for pharmaceutical scientists who are not familiar with polymer science, summarizes the characteristic properties of each architecture useful for drug delivery applications, and covers recent advances in drug delivery relevant to polymer architecture.     

药物传递系统和传递策略

一种药物被聚合物或脂质体包裹或吸附,其使用安全性和效率能被极大地改善,并且使新的治疗成为可能。这将为促进可降解材料的设计智能化传递系统和探讨体内各类传递途径等主动性研究提供了原动力。     

Schizophrenia and Drug Delivery Systems

Abstract

Schizophrenia is a severe non-curable illness of the brain with serious consequences if not properly treated and kept under control. Antipsychotic drugs have revolutionised the therapy and management of schizophrenia. However, patient compliance rates are notoriously poor due to the nature of the disease and troublesome side-effects, and are major causes of symptom recurrence. Although some new antipsychotic agents have been marketed to offer broader efficacy with much reduced side-effect profiles, the drug delivery systems for antipsychotics are still in the stage of conventional dosage forms, such as tablets, capsules and solutions, and need to be dosed at the frequency of 2-4 times daily. Doubtless, novel drug delivery systems, such as sustained and controlled release systems, will be useful for antipsychotics. They should reduce the frequency of dosing, enhance drug bioavailability and improve patient compliance. In this article, the specificity and characterisation of schizophrenia and pathophysiology, drug therapy, and the development and future prospects of neuroleptic drug delivery systems are reviewed.