Review on brain-targeted drug delivery

– The Overall prevalence rate for CNS pathology has demonstrated that approximately 1.5 billion people undergoing from disorders of central nervous system. The most distressing fact about delivery of drugs to the CNS is the presence of blood brain barrier that have a tendency to impair the drug distribution and denotes the major impediment for the development of CNS drugs. Neuropeptides and many drugs which are hydrophilic in nature, possibly will encompass the intricacy while passing the blood brain barrier. The net amount of delivered drug (medicinal agent) and its capability to gain access to the pertinent target sites are the main considering points for CNS drug development. In order to distribute the drugs into the CNS via passing the blood brain barrier, many new emerging approaches have been developed for example Magnetic drug targeting, chemical delivery Systems, Drug carrier systems (antibodies, liposomes or Nanoparticles). Among drug carrier system, Nanoparticles exhibit an impressive attention in the field of targeted drug delivery system because of possessing solid colloidal particles with a size range between 1-1000nm. Gradual drug release reduced peripheral toxicity and potential to target specific brain sites by crossing the blood brain barrier are major benefits contributed by Nanoparticles. In this review we will discuss the methodologies for targeting the brain site.

Frontiers in Veterinary Science

The blood-brain barrier (BBB) presents a formidable obstacle to the effective delivery of systemically administered pharmacological agents to the brain, with ~5% of candidate drugs capable of effectively penetrating the BBB. A variety of biomaterials and therapeutic delivery devices have recently been developed that facilitate drug delivery to the brain. These technologies have addressed many of the limitations imposed by the BBB by: (1) designing or modifying the physiochemical properties of therapeutic compounds to allow for transport across the BBB; (2) bypassing the BBB by administration of drugs via alternative routes; and (3) transiently disrupting the BBB (BBBD) using biophysical therapies. Here we specifically review colloidal drug carrier delivery systems, intranasal, intrathecal, and direct interstitial drug delivery methods, focused ultrasound BBBD, and pulsed electrical field induced BBBD, as well as the key features of BBB structure and function that are the mechanistic...

Pharmaceutics

The blood–brain barrier (BBB) has shown to be a significant obstacle to brain medication delivery. The BBB in a healthy brain is a diffusion barrier that prevents most substances from passing from the blood to the brain; only tiny molecules can pass across the BBB. The BBB is disturbed in specific pathological illnesses such as stroke, diabetes, seizures, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. The goal of this study is to offer a general overview of current brain medication delivery techniques and associated topics from the last five years. It is anticipated that this review will stimulate readers to look into new ways to deliver medications to the brain. Following an introduction of the construction and function of the BBB in both healthy and pathological conditions, this review revisits certain contested questions, such as whether nanoparticles may cross the BBB on their own and if medications are selectively delivered to the brain by deliberately target...

Recent Patents on Nanomedicine, 2014

The delivery of drug to central nervous system is becoming a challenging task as it has to overcome various obstacles present in the brain i.e. blood brain barrier and blood cerebrospinal fluid barrier. Blood brain barrier is the barrier that comes in the way of central nervous system drug delivery. Brain targeting opens new avenues for researchers to look forward for better advancement so that patients suffering from brain diseases can have a feeling of relief. The current challenge that has to be faced is to create strategies of drug targeting that will permit the drug molecule to pass through blood brain barrier in an effective manner and this review deals with these strategies to safely enhance brain targeted drug delivery. This article reviews the various approaches of brain targeting in terms of various patents and commercial value.

Many pharmaceuticals cannot access brain, though, has potential for treatment and this is mainly due to the potential blood brain barrier. To have a successful delivery, the challenges of anatomical and physiological aspects of those barriers need to be addressed. Though a considerable efforts were made in convincing those barriers, still designing a suitable delivery remains a major challenge. This review lists various strategies for the drug delivery to the brain. Sophisticated approaches like intracerebral delivery, intranasal delivery, barrier disruptions, receptor mediated transport, prodrugs, chemical drug delivery and many more were discussed. Limitations of some strategies were also discussed. Understanding the strategies along with the suitability of the therapeutic agent to undergo those strategic modifications would certainly promises the success of a brain drug delivery program. This a review made here would help the researcher in understanding the barrier and further modifying the therapeutic agent for the suitable drug or delivery.

Cns Drugs, 2009

Being the most delicate organ of the body, the brain is protected against potentially toxic substances by the blood-brain barrier (BBB), which restricts the entry of most pharmaceuticals into the brain. The developmental process for new drugs for the treatment of CNS disorders has not kept pace with progress in molecular neurosciences because most of the new drugs discovered are unable to cross the BBB. The clinical failure of CNS drug delivery may be attributed largely to a lack of appropriate drug delivery systems. Localized and controlled delivery

Current Topics in Medicinal Chemistry, 2009

This paper provides a mini-review of some recent approaches for the treatment of brain pathologies examining both medicinal chemistry and pharmaceutical technology contributions. Medicinal chemistry-based strategies are essentially aimed at the chemical modification of low molecular weight drugs in order to increase their lipophilicity or the design of appropriate prodrugs, although this review will focus primarily on the use of prodrugs and not analog development. Recently, interest has been focused on the design and evaluation of prodrugs that are capable of exploiting one or more of the various endogenous transport systems at the level of the blood brain barrier (BBB). The technological strategies are essentially non-invasive methods of drug delivery to malignancies of the central nervous system (CNS) and are based on the use of nanosystems (colloidal carriers) such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, polymeric micelles and dendrimers. The biodistribution of these nanocarriers can be manipulated by modifying their surface physico-chemical properties or by coating them with surfactants and polyethylene-glycols (PEGs). Liposomes, surfactant coated polymeric nanoparticles, and solid lipid nanoparticles are promising systems for delivery of drugs to tumors of the CNS. This mini-review discusses issues concerning the scope and limitations of both the medicinal chemistry and technological approaches. Based on the current findings, it can be concluded that crossing of the BBB and drug delivery to CNS is extremely complex and requires a multidisciplinary approach such as a close collaboration and common efforts among researchers of several scientific areas, particularly medicinal chemists, biologists and pharmaceutical technologists.

2020

There are three types of barrier present in central nervous system such as Blood Brain Barrier, Blood Cerebro-Spinal Fluid Barrier, and Blood– Arachnoid Barrier. BBB is the very tough barrier for the transport of drugs to brain. For the treatment of various diseases related to CNS like brain cancer, Alzheimer disease, parkinson’s disease, epilepsy, psychiatric disorders or neurodegenerative diseases, different types of drugs are available. But they have some lacuna for transport of drug though these barriers and reaching drug to the target site. This review is one of the attempts to amend the recent information on cellular structure of BBB as well as different procedures planned to cross it. Different strategies and approaches are utilized to improve brain targeted drug delivery system. Lipophilicity of drug can be increased by chemical modification, while colloidal carriers like Nanoparticles, Dendrimers, Lipososmes , Nanogels enhances properties and therapeutic effect of drug in b...

Journal of Drug Delivery and Therapeutics

A targeted drug delivery system is based on a technique that continuously administers a predetermined dosage of a therapeutic agent to a sick location of the body. The targeted drug delivery goal is to raise the relative amount of the treatment in the target tissues while lowering it in the non-target tissues. This technique's intrinsic benefit has been reduced drug dose and adverse effects. Drug targeting in the brain is one of the most challenging issues in pharmaceutical research because the blood-brain barrier acts as an impermeable barrier for systemically delivered therapeutics and the brain extracellular matrix contributes to the poor distribution of locally delivered drugs. In the treatment of various Central nervous system (CNS) diseases, general approaches that can improve drug delivery to the brain are of great interest. Drugs are less harmful and more effective when they are administered close to where they would be most effective. Extreme research studies have recen...

The objective of this article is to provide the reader with an update on some research highlights from the past to the present, as well as future possibilities to achieve improved delivery of drugs across the blood-brain barrier (BBB). In the past, dye studies confirmed the presence of the BBB and blood-cerebrospinal fluid barriers, which seem to play a major role in transporting drug molecules for the treatment of life-threatening diseases such as brain cancer and Alzheimer's. Presently, transportation mechanisms such as simple diffusion, carrier-mediated, absorptive-mediated, and receptor-mediated transcytosis are extensively used for BBB uptake of drug molecules. The spectrum of future neuropharmaceuticals falling into these categories ranges from peptides to nucleotide-based drugs as well as gene and stem cell deli very agents, and is increasing at a rapid rate with promising results. There has also been considerable progress in the development of quantitative methods to examine BBB permeability in humans and animals. Currently, intravenous administration and in situ brain perfusion techniques are the most versatile and sensitive methods to measure transport into the brain. This article also reviews the various methodologies available for assessing the transfer of drug molecules undergoing significant uptake through the BBB in vivo.