CNS Drug Delivery Systems: Novel Approaches

Abstract

The brain is a delicate organ, and nature has very efficiently protected it. The brain is shielded against potentially toxic substances by the presence of two barrier systems: the blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB). Unfortunately, the same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Despite aggressive research, patients suffering from fatal and/or debilitating central nervous system (CNS) diseases, such as brain tumours, HIV encephalopathy, epilepsy, cerebrovascular diseases and neurodegenerative disorders, far outnumber those dying of all types of systemic cancers or heart diseases. The abysmally low number of potential therapeutics reaching commercial success is primarily due to the complexity of the CNS drug development. The clinical failure of many probable candidates is often, ascribable to poor delivery methods which do not pervade the unyielding BBB. It restricts the passive diffusion of many drugs into the brain and constitutes a significant obstacle in the pharmacological treatment of central nervous system (CNS) disorders. General methods that can enhance drug delivery to the brain are, therefore, of great pharmaceutical interest. Various strategies like non-invasive methods, including drug manipulation encompassing transformation into lipophilic analogues, prodrugs, chemical drug delivery, carrier-mediated drug delivery, receptor/vector mediated drug delivery and intranasal drug delivery, which exploits the olfactory and trigeminal neuronal pathways to deliver drugs to the brain, are widely used. On the other hand the invasive methods which primarily rely on disruption of the BBB integrity by osmotic or biochemical means, or direct intracranial drug delivery by intracerebroventricular, intracerebral or intrathecal administration after creating reversible openings in the head, are recognised. Extensive review pertaining specifically, to the patents relating to drug delivery across the CNS is currently available. However, many patents e.g. US63722506, US2002183683 etc., have been mentioned in a few articles. It is the objective of this article to expansively review drug delivery systems for CNS by discussing the recent patents available.

Inhalation of growth factors and apo-transferrin to protect and repair the hypoxic-ischemic brain

“…A wide range of studies has explored the transport of various drugs from the nasal cavity to the brain and, although most of them have been conducted in rat models, studies in mice, rabbits and monkeys have also been reported. INA has not only been used in the basic research field [5][6][7][8], but has also found applications in human health [9,10].…”

Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

“…Moreover, failure of ART penetration into sanctuaries of persistent viral replication including the lymphoreticular and central nervous systems, and a range of secondary drug-induced toxicities further highlight the limitations of chronic drug treatment regimens. [6][7][8][9][10] One approach to address such limitations is through long-acting antiretroviral drug nanoformulations with half-lives measured in week(s) rather than hours. To this end, improvements in drug pharmacodynamics were described for ART nanoformulations (nanoART).…”

Ear as an alternative way for brain drug targeting: An Overview

“…As the surface of BCSFB faces the ventricle that is filled with CSF, not the blood [7], this, in combination with the high turnover rate of CSF, leads to continuously flushing the injected drug (i.e. those injected into the ventricle) back to the blood [8]. The BBB, therefore, is universally considered as the most important barrier in preventing molecules from reaching the brain parenchyma via extensive branches of blood capillary networks.…”

“…Importantly, samples for the pharmacokinetic study described therein were extracted from the fourth ventricle of the brain [7]. This indicates that drugs delivered via the inner ear are distributed in the brain's fourth ventricle and suggests that the delivery via the inner ear may be used in targeting the tissue of the brain [8] inside and at the vicinity of the fourth ventricle. One such therapeutic application is in treatment of pain.…”