Nanoparticles as a Carrier System for Drug Delivery Across Blood Brain Barrier (original) (raw)
Related papers
The potential for nanoparticle-based drug delivery to the brain: overcoming the blood–brain barrier
Expert Opinion on Drug Delivery, 2009
The development of blood-brain barrier (BBB)-targeting technologies is a very active field of research: targeting therapeutic actives to the central nervous system by means of systemic administration means crossing the BBB, and this is now one of the most challenging problems in drug development. The BBB is a unique regulatory system that protects the brain environment by separating it from direct contact with the circulating blood. In doing so, it impedes at the same time the access of a large number of diagnostic and therapeutic agents into the brain parenchyma. One of the possibilities of bypassing this barrier relies on specific properties of nanoparticulate vectors designed to interact with BBB-forming cells at a molecular level, as a result of which the transport of drugs or other molecules (such as nucleic acids, proteins or imaging agents) could be achieved without interfering with the normal function of the brain. This article summarises several recent example applications, presents emerging work and highlights the directions for further developments in this area.
Nanoparticle Technology for Drug Delivery Across the Blood-Brain Barrier
Nanoparticles (NP) are solid colloidal particles ranging in size from 1 to 1000 nm that are utilized as drug delivery agents. The use of NPs to deliver drugs to the brain across the blood-brain barrier (BBB) may provide a significant advantage to current strategies. The primary advantage of NP carrier technology is that NPs mask the blood-brain barrier limiting characteristics of the therapeutic drug molecule. Furthermore, this system may slow drug release in the brain, decreasing peripheral toxicity. This review evaluates previous strategies of brain drug delivery, discusses NP transport across the BBB, and describes primary methods of NP preparation and characterization. Further, influencing manufacturing factors (type of polymers and surfactants, NP size, and the drug molecule) are detailed in relation to movement of the drug delivery agent across the BBB. Currently, reports evaluating NPs for brain delivery have studied anesthetic and chemotherapeutic agents. These studies are reviewed for efficacy and mechanisms of transport. Physiological factors such as phagocytic activity of the reticuloendothelial system and protein opsonization may limit the amount of brain delivered drug and methods to avoid these issues are also discussed. NP technology appears to have significant promise in delivering therapeutic molecules across the BBB.
Overcoming blood–brain barrier transport: Advances in nanoparticle-based drug delivery strategies
Materials Today, 2020
The blood-brain barrier (BBB), a unique structure in the central nervous system (CNS), protects the brain from bloodborne pathogens by its excellent barrier properties. Nevertheless, this barrier limits therapeutic efficacy and becomes one of the biggest challenges in new drug development for neurodegenerative disease and brain cancer. Recent breakthroughs in nanotechnology have resulted in various nanoparticles (NPs) as drug carriers to cross the BBB by different methods. This review presents the current understanding of advanced NP-mediated non-invasive drug delivery for the treatment of neurological disorders. Herein, the complex compositions and special characteristics of BBB are elucidated exhaustively. Moreover, versatile drug nanocarriers with their recent applications and their pathways on different drug delivery strategies to overcome the formidable BBB obstacle are briefly discussed. In terms of significance, this paper provides a general understanding of how various properties of nanoparticles aid in drug delivery through BBB and usher the development of novel nanotechnology-based nanomaterials for cerebral disease therapies.
Nano carriers for drug transport across the blood-brain barrier
Journal of drug targeting, 2016
Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-...
Drug Permeation across the Blood-Brain Barrier: Applications of Nanotechnology
British Journal of Medicine and Medical Research, 2015
The blood-brain barrier (BBB) is a neurobiological frontier that isolates brain tissues from the blood vascular system. Its main role is to protect the brain and the central nervous system from external fluctuations in hormones, nutrients and drugs, while allowing the passage of water and small lipophilic molecules. Diffusion across the BBB can occur through several biological mechanisms, but the most common one is simple diffusion, which mainly depends on the size, lipid solubility and concentration gradient of the molecule. Because of the highly dense network of capillary endothelium cells found in the BBB, most of the drugs are not able to cross this physiological barrier. Delivering therapeutic agents to the brain is thus a big challenge, which may prevent treatment of important neurological diseases. In order to overcome this difficulty, researchers have used nanotechnology to help the passage of drugs across the BBB. Nanotechnology has significantly contributed to the field of biotechnology by improving the strategies for drug delivery, and by providing novel carriers for safe and effective brain targeting. The aim of this review is to BJMMR, 6(6): 547-556, 2015; Article no.BJMMR.2015.232 548 discuss in more details the anatomical structure and the functions of the BBB, as well as its significance in neurological diseases. A closer look will be given at the transport mechanisms across the BBB. This review finally explores the most recent advances in the field of nanotechnology for drug delivery in the brain, and gives meaningful examples of delivery systems developed including the micelles, liposomes, dendrimers, microcapsules and polymeric nanoparticles.
Multifunctional Nanoparticles for Successful Targeted Drug Delivery across the Blood-Brain Barrier
Molecular Insight of Drug Design
The blood-brain barrier (BBB) is the major problem for the treatment of brain diseases because we need to be able to deliver drugs from the vascular system into the central nervous system (CNS). There are no drug therapies for a wide range of CNS diseases and these include neurodegenerative diseases such as Alzheimer's and Parkinson's diseases and cerebral ischemia. Therefore, the focus of this chapter is to discuss how nanoparticles (NPs) can be modified to transport different drug molecules for the treatment of brain diseases. In essence, NPs' surface can be functionalized with molecules such as peptides, antibodies and RNA aptamers and these macromolecules can be attached to the receptors present at the BBB endothelial cell surface, which allows the NPs cross the barrier and subsequently deliver pharmaceuticals to the brain for the therapeutic and/or imaging of neurological disorders. In fact, part of the difficulty in finding an effective treatment for these CNS disorders is that there is not yet an efficient delivery method for drug delivery across the BBB. However, over the last several years, researches have started to understand some of the design rules to efficiently deliver NPs to the brain.
Brain-targeted nanoparticles to overcome the blood-brain barrier
Journal of Pharmaceutical Technolgy, 2020
The blood-brain barrier is one of the most complicated barrier to pass for therapeutic drugs. Because of the structure of the blood-brain barrier, only a few small molecules with appropriate lipophilicity, molecular weight, and charge can penetrate through the blood-brain barrier and pass in the central nervous system. Because of this unique property, blood-brain barrier is still a major problem for the treatment of central nervous system diseases. In the last decades, many strategies to overcome this barrier have been investigated. Compared to other drug delivery strategies, due to the reduced side effects and no requirement for surgical operations, brain targeted nanoparticle is one the most promising and popular strategy used do deliver drugs to the brain. Many in vitro and in vivo preclinical studies have been conducted to determine optimum brain targeted nanoparticles. These studies were reported that characteristics of nanoparticles such as particle size, zeta potential, and targeting ligand are critical to achieving the goals. In this review, first of all, the structure of the blood-brain barrier and possible causes of blood-brain barrier disruption were summarized. Later, previous strategies of brain targeted drug delivery and characteristic prosperities for optimized brain-targeted nanoparticles were evaluated. Moreover, different strategies, such as focus ultrasound, which can increase the effectiveness of nanoparticular system applications, are mentioned.
Pharmaceutical Research, 2014
The blood-brain barrier is a unique cell-based restrictive barrier that prevents the entry of many substances, including most therapeutics, into the central nervous system. A wide range of nanoparticulate delivery systems have been investigated with the aim of targeting therapeutics (drugs, nucleic acids, proteins) to the brain following administration by various routes. This review provides a comprehensive description of the design and formulation of these nanoparticles including the rationale behind individual approaches. In addition, the ability of currently available in-vitro BBB models to accurately predict the in-vivo performance of targeted nanoparticles is critically assessed.
Transport of drugs across the blood–brain barrier by nanoparticles
Journal of Controlled Release
The central nervous system is well protected by the blood-brain barrier (BBB) which maintains its homeostasis. Due to this barrier many potential drugs for the treatment of diseases of the central nervous system (CNS) cannot reach the brain in sufficient concentrations. One possibility to deliver drugs to the CNS is the employment of polymeric nanoparticles. The ability of these carriers to overcome the BBB and to produce biologic effects on the CNS was shown in a number of studies. Over the past few years, progress in understanding of the mechanism of the nanoparticle uptake into the brain was made. This mechanism appears to be receptor-mediated endocytosis in brain capillary endothelial cells. Modification of the nanoparticle surface with covalently attached targeting ligands or by coating with certain surfactants enabling the adsorption of specific plasma proteins are necessary for this receptor-mediated uptake. The delivery of drugs, which usually are not able to cross the BBB, into the brain was confirmed by the biodistribution studies and pharmacological assays in rodents. Furthermore, the presence of nanoparticles in the brain parenchyma was visualized by electron microscopy. The intravenously administered biodegradable polymeric nanoparticles loaded with doxorubicin were successfully used for the treatment of experimental glioblastoma. These data, together with the possibility to employ nanoparticles for delivery of proteins and other macromolecules across the BBB, suggest that this technology holds great promise for non-invasive therapy of the CNS diseases.