ABSTRACT Intranasal delivery provides a practical, noninvasive method of bypassing the blood-brain barrier (BBB) to deliver therapeutic agents to
Prodrug Strategies for Brain Targeted Delivery of Antiparkinson Agents
The brain is one of the least accessible organs for the delivery of drugs. The mechanisms that protect the brain from foreign substances also restrict the entry of many therapeutic agents in the treatment of fatal CNS diseases such as brain tumors, HIV, encephalopathy, epilepsy, cerebro-vascular diseases and neurodegenerative disorders. Despite its relatively high blood flow, blood–brain barrier (BBB) is a strong hurdle that has to be crossed for efficient delivery of any bioactive agent into the brain.
The development of new drugs for the brain has not kept pace with progress in the molecular neurosciences, because the majority of large-molecule drugs and greater than 98% of small-molecule drugs do not cross the BBB. More than 99% of worldwide CNS drug development is devoted to CNS drug discovery with <1% of the efforts devoted to CNS drug delivery.
The available strategies for CNS drug delivery include intra-ventricular drug infusion, intra-cerebral implants, BBB disruption, liposomal delivery, carrier /receptor-mediated transport and prodrugs.
Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, characterized by bradykinesia, postural instability, rigidity and tremor due to specific loss of dopamine neurons in the substantia nigra pars compacta. Dopamine deficiency appears to be responsible for the motor deficits of the disorder but PD cannot be treated directly with dopamine or related catecholamines due to their extensive first pass metabolism and poor permeability across the BBB. L-dopa, a prodrug of dopamine, still remains the most clinically useful drug for treatment of PD but suffers from many drawbacks. To improve pharmacological and pharmacokinetic properties of dopamine and L-dopa, numerous attempts have been made for their targeted delivery to brain through prodrug approach.
This presentation will highlight current status of antiparkinson therapy, drawbacks of BBB, need for brain targeted delivery, various prodrug strategies and recent trends for efficient delivery of antiparkinson drugs to brain.
Click to see next slide
Treating CNS diseases is particularly challenging because a variety of formidable obstacles often impede drug delivery to brain and spinal cord.
Recent advances in the use of nano particles, liposomes, colloidal drug carriers and micelles in brain targeted drug delivery system
Target delivery of drug molecules to brain is one of the most challenging research areas in pharmaceutical sciences. The blood-brain barrier (BBB) represents an insurmountable obstacle for a large number of drugs, including antibiotics, antineoplastic agents, and a variety of central nervous system (CNS)-active drugs, especiallyneuropeptides. Therefore, various strategies have been proposed to improve the delivery of different drugs to this tissue which includesliposomes, colloidal drug carriers, micelles, chimeric peptide technology, intranasal and olfactory route of administration andnano technology.
The BBB is located at the level of brain capillaries, where there is a convergence of different cell types. The brain micro vessel endothelial cell (BMEC) that form the BBB, display important morphological characteristics such as the presence of tight junctions between the cells, the absence of fenestrations and a diminished pinocytics activity, that together help to restrict the passage of compounds from the blood into the extra cellular environment of the brain
The present topic deals in brief about the status of the BBB. The first part of this topic aims to review the strategies developed to circumvent the BBB and deliver drugs into the brain. The use of nano technology and liposomes are discussed which are crucial parts of this power point presentation as mainly used to target various CNS disorders. The later part contains future aspects of brain drug targeting...
Our power point presentation deals with Brain targeting technology, Colloidal drug carriers, Micelles, Liposomes, nano Technology
Peptides are key regulators in cellular and intercellular physiological responses and possess enormous promise for the treatment of pathological
Intranasal drug delivery is one of the best drug deliveries which target CNS.
The mechanism for the accumulation of itraconazole (ITZ) in its elimination from the brain was studied in rats and mice.