Polymeric Nanoparticles Properties and Brain Delivery (original) (raw)
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ACS Chemical Neuroscience, 2017
The window of neurological maladies encompasses 600 known neurological disorders. In the last few years, an inordinate upsurge in the incidences of neuronal ailments with increased mortality rate has been witnessed globally. Despite noteworthy research in the discovery and development of neural therapeutics, brain drug delivery still encounters limited success due to meager perviousness of most of the drug molecules through the blood-brain barrier (BBB), a tight layer of endothelial cells that selectively impedes routing of the molecules across itself. In this review, we have tried to present a comprehensive idea on the recent developments in nanoparticle based BBB delivery systems, with a focus on the advancements in receptor targeted polymeric nanoparticles pertaining to BBB delivery. We have also attempted to bridge the gap between conventional brain delivery strategies and nanoparticle based BBB delivery for in-depth understanding. Various strategies are being explored for simplifying delivery of molecules across the BBB, however they have their own limitations such as invasiveness, need for hospitalization and surgery. Introduction of nanotechnology can impressively benefit the brain drug delivery. Though, many nanoparticles are being explored, but there are still several issues that need to be analyzed scrupulously before a real and efficient BBB traversing nanoformulation is realized.
Polymeric nanoparticles for the drug delivery to the central nervous system
Expert Opinion on Drug Delivery, 2008
Background : Nanoparticulate polymeric systems (nanoparticles [Np]) have been widely studied for the delivery of drugs to a specific target site. This approach has been recently considered for the therapy of brain diseases. The major problem in accessing the CNS is linked to the presence of the blood -brain barrier. Objective : The present review deals with the different strategies that have been developed in order to allow Np drug carriers entry into the CNS parenchyma. Among these, the use of magnetic Np, Np conjugation with ligands for blood -brain barrier receptors, with antibodies, and the use of surfactants have been considered. Methods : All the literature available is reviewed in order to highlight the potential of this drug delivery system to be used as a drug carrier for the treatment of CNS pathologies. Conclusions : Polymeric Np have been shown to be promising carriers for CNS drug delivery due to their potential both in encapsulating drugs, hence protecting them from excretion and metabolism, and in delivering active agents across the blood -brain barrier without inflicting any damage to the barrier. Different polymers have been used and different strategies have been applied; among these, the use of specific ligands to enhance the specificity of drugs delivered to the CNS has recently been considered. At present, clinical trials are being conducted appeared for the use of these drug carriers but none related to the treatment of CNS diseases.
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.
Polymeric nanocarriers for controlled and enhanced delivery of therapeutic agents to the CNS
2012
The development of drug-loaded nanocarriers to vehiculate active principles to a target site is an emerging topic in the field of nanoscience. Recently, several systems have been developed for the treatment of various neurological disorders. The main advantages of using nanocarriers are: protection of the active principle from the biological environment; enhanced transport through biological barriers; and targeted transport to specific cells or tissues, with the final goal to improve efficacy and safety of the pharmacological treatment. All these characteristics are related to the extreme versatility of nanocarriers, which can be functionalized and designed to be responsive to external stimuli [1, 2] . Nanocarriers provide a promising approach for the delivery of various agents, including drugs [3], proteins Polymeric nanocarriers for controlled and enhanced delivery of therapeutic agents to the CNS Polymeric nanocarriers are versatile structures that can be engineered to obtain high drug loading, good delivery yields and tunable release kinetics. Moreover, the particle surface can be modiied for selective targeting of organs or tissues. In particular, polymeric nanocarriers can be conjugated with functional groups promoting translocation through the blood-brain barrier, thus providing a promising system to deliver therapeutic agents and/or diagnostic probes to the brain. Here we review recent literature on the preparation and characterization of polymeric nanoparticles as potential agents for drug delivery to the CNS, with an emphasis on materials chemistry and functionalization strategies for improved selectivity and delivery. Finally, we underline the immunotoxicological aspects of this class of nanostructured materials in view of potential clinical applications.
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.
Drug transport to brain with targeted nanoparticles
NeuroRx, 2005
Summary: Nanoparticle drug carriers consist of solid biodegradable particles in size ranging from 10 to 1000 nm (50–300 nm generally). They cannot freely diffuse through the blood-brain barrier (BBB) and require receptor-mediated transport through brain capillary endothelium to deliver their content into the brain parenchyma. Polysorbate 80-coated polybutylcyanoacrylate nanoparticles can deliver drugs to the brain by a still debated mechanism. Despite interesting results these nanoparticles have limitations, discussed in this review, that may preclude, or at least limit, their potential clinical applications. Long-circulating nanoparticles made of methoxypoly(ethylene glycol)- polylactide or poly(lactide-co-glycolide) (mPEG-PLA/PLGA) have a good safety profiles and provide drug-sustained release. The availability of functionalized PEG-PLA permits to prepare target-specific nanoparticles by conjugation of cell surface ligand. Using peptidomimetic antibodies to BBB transcytosis receptor, brain-targeted pegylated immunonanoparticles can now be synthesized that should make possible the delivery of entrapped actives into the brain parenchyma without inducing BBB permeability alteration. This review presents their general properties (structure, loading capacity, pharmacokinetics) and currently available methods for immunonanoparticle preparation.
Nanoparticles as a Carrier System for Drug Delivery Across Blood Brain Barrier
Current drug metabolism, 2017
Brain, the center of the nervous system and an integral part the body, is protected by two anatomical and biochemical dynamic barriers- Blood-Brain Barrier (BBB) and Blood-Cerebrospinal Fluid Barrier (BCSFB). Blood-Brain Barrier is a highly complex multi-cellular organized structure that protects the brain from harmful substances and invading organisms from the bloodstream and thus protecting it from diseases and injuries. However, it also significantly precludes the delivery of drug to the brain, thus, preventing treatment of a number of neurological disorders. Even though various traditional approaches such as Intra-Cerebro-Ventricular (ICV) injection, use of implants, disruption of BBB and use of prodrugs have shown some success to overcome this barrier, researchers are continuously working for alternatives for improved drug delivery to the brain. Recent advances in the field of nanotechnology offer an appropriate solution for drug delivery problems associated with these approach...
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-...
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.