1
Department of Pharmacy, School of Medical and Allied Sciences,Galgotias University, Yamuna Expressway, Greater Noida, U.P, India
Corresponding author details:
Anchal Tyagi
Department of Pharmacy
School of Medical and Allied Sciences, Galgotias University
Greater Noida, U.P,India
Copyright:
© 2018 Tyagi A, et al. This is
an open-access article distributed under the
terms of the Creative Commons Attribution 4.0
international License, which permits unrestricted
use, distribution, and reproduction in any
medium, provided the original author and source
are credited.Vium mor li, poracidisus es condam
Brain targeting is a bottle neck for the drug discovery scientist, due to its special
protective system. The Blood Brain Barrier (BBB) and the blood cerebrospinal fluid barrier
(BCFB) are not only protective barriers of the CNS but it can maintain the neuronal activity
and functioning of the CNS This body protective system makes difficult to target the brain
for the treatment of many CNS disorder. In the process of the better delivery system for the
CNS many development has been made so far, but in the present scenario the emphasis on
the eye has been in the developing stage. The eye is very sensitive organ of the body. Brain
targeting through the ocular route is an intense task. Here in the various approaches has
been summarized in three categories: Noninvasive, invasive and alternative routes of CNS
delivery, moreover the factors affecting blood brain barrier been discussed.
Brain and drug targeting; Ophthalmic route; Blood Brain Barrier
The targeted delivery for central nervous system can be achieved by direct administration
of the drugs in to the CNS [1]. Blood Brain Barrier (BBB) acts as a big obstacle in the
distribution of drugs in to the CNS. The BBB plays major role in the selectivity of many of the
drugs; moreover, it is well known that the hydrophilic drugs possess low affinity towards
the BBB as compare to hydrophobic drugs. Brain targeting drug must cross the BBB or
bypass the barrier, which will effect brain in efficient manner [2]. The BBB and BCSFB do
not only protect the CNS against infectious agents and toxic agents, but also create an effect
to the systemic drug delivery into the CNS [3]. The BBB and BCSFB functions are controlling
the transfer of molecules between the blood and brain parenchyma and Cerebrospinal Fluid
(CSF) [4]. It has been observed that CNS disorder is a difficult task due to the BBB and
BCSFB. The Blood Brain barrier helps in transporting water and lipid soluble substances
from blood circulation into CNS [5]. In the recent scenario, it is important to look into the
most effective delivery system an ocular route for targeting CNS is important [3,4].
BBB acts as a dynamic interface. The approaches of the blood brain barrier have
been used to increase the brain penetration. BBB is a major offend toward the brain
targeted drug delivery [6]. The BBB protect the CNS from harmful substance [7]. The BBB
maintained the volumetric and ionic environments and create the interference for systemic
drug delivery to the CNS. The BBB plays important role in the conveying of lipid and water
soluble substances from blood circulation into CNS [8]. The drug crosses BBB through the
combination of endogenous compounds [9]. The low molecular mass (< 400-500 Da) with
high lipid solubility substances have high capability to crossed the BBB, this phenomena
is utilized to deliver the drug into the brain [5,10]. The BBB poses some differentiating
features, which causes highly efficacious obstacle to the entry of chemical compounds
into CNS [11]. It has the valuable ability to reduce and separate the human brain from
circulatory network and allow only conveying of molecules that play the functional activity
of brain [12]. The capillary endothelium of BBB acts as a permeability barrier [13]. The BBB
has been started the creative path or convenience for better drug delivery to the brain [14].
Three factors mostly affect the blood brain barrier.
There are some factors of ocular drug delivery that affect the
pharmacokinetics of the drugs and provide obstacle to target the
brain through ocular route. The blood ocular barrier also provides
protection from xenobiotics from the blood. Blood ocular barrier
are two types 1) Blood-retina Barrier (BRB) and 2) Blood-aqueous
Barrier (BAB) [17]. These barrier play first protection layer, however,
the crossing this barrier, drug can be easily reached to the choroid
and retina. This barrier is necessary for specific targeting. The brain
disorders which are refractory to small drug molecule therapies areCVS disorders, neurodegenerative disorders (Parkinson’s disease and
Alzheimer disease) and inflammatory disorders (Brain/spinal cord
strokes) [18]. Approaches across the brain barriers are mentioned
in Table 1.
Table 1: Different approaches across the brain barriers [19]
Biological Method: The delivery of chimeric peptides by the receptor or vector is based on the use of a pharmaceutical peptide (Nontransferable). They joined with a transferable peptide which endures transcytosis interceded by receptor through BBB [21]. When the receptor gets bound to the receptor endocytosis gets initiated [22]. The nanoparticles avidness gets tuned to the focused receptor then its efficiency of this transcytosis regulated by receptor can be controlled. There is another technology which is regulated by cell penetrating peptide which is used to augment the delivery in CNS [23]. They operate through from unique mechanism which is receptor independent to interact with the surface of cells. They are also capable of transferring the molecules through the cell membrane which are attached to them. In process of target delivery many peptides have been used, but among the various peptides used, including Human Immuno Deficiency Virus type 1, herpes simplex virus type 1 etc., Trans-Activating Transcriptional (TAT) activator is the most reviewed [24].
Colloidal Drug Carriers: A colloid is a suspension of dispersed particles or droplets. Its range of particle diameter is about 1 to 1000 nm [25]. The colloidal drug carriers are liposomes, dendrimers, nanoparticles, micelles and emulsions. In colloidal drug carrier nanomedicines can go across the BBB by endocytosis and have been observed during the preclinical study for CNS conditions like HIV encephalopathy, acute ischemic stroke, brain tumors and Alzheimer’s disease [26]. The blood distribution of colloidal particles influencing by the various factors like particle size, stability and surface affinity [27]. So far some colloidal carriers have been adopted for CNS delivery; they are single-walled carbon nanotubes and Polyethyleneimine (PEI) [28]. PEI is an organic polymeric molecule with a high cationic charge density due to the presence of multiple amino groups. Carbon nanotubes and PEI derivatives have been critically evaluated for gene transfer.
Intracerebral implants: Intracerebral implants is a highly traumatic drug delivery strategy which contain matrix and biodegradable polymer reservoirs. The polymer-controlled implants the strategy involves many advantages of the CNS delivery like low peak drug release limits tissue damage, biocompatible, low invasiveness, tunable release properties, sustained drug delivery, and localized delivery [29]. The disadvantage includes dosage limited by implant size and poor drug penetration. Intracerebral implants are also used in chemotherapeutic [30].
Intraventricular delivery/interstitial delivery: The blood brain barriers deliver the drug directly into the Intraventricular delivery or the interstitial delivery system. The anticancer drug has been administered locally to obtain the drug concentration for longer period. [31,32]. In various clinical trials, some drugs like methotrexate and nitrosourea were used. The disadvantages of this strategy are catheter obstruction, CNS infection and inadequate drug distribution [33].
Biological tissue delivery: In this tissue implants delivery technique into the brain is used to modulate naturally secreted therapeutic agent. This tissue delivery is used for the treatment of Parkinson’s disease [34]. Transplanted tissue cannot be present to a lack of neovascular innervations. In these techniques foreign tissue is improved for culturing distinct cell types.
Blood Brain Barrier Disruption (BBBD): Blood brain barrier
disruption strategy is an independent part of invasive techniques.
BBBD therapy is an intensive and effective way of sending medication
to brain tumors. In BBBD hyperosmolar mannitol solution is used as
additive. BBBD can increase the permeability of the BBB by shrinkage
of cerebrovascular endothelial cells followed by production of
disrupted inter-endothelial [35]. The BBB enduring to this agent,
such as lactamide, saline, urea, radiographic contrast agents,
hyperosmolar solutions of Arabians and mannitol.
The alternate approach for CNS can be characterized in to intranasal and iontophoric delivery system.
Brain targeting is a challenging task as delivered drug gets
prohibited across the brain. The suitable and effective approach of
drug delivery to the brain may facilitate the drug to the brain for
effective CNS treatment. An improvement in the passive permeation
of the BBB has an important role to play the drug delivery science.
In search of better targeted delivery, the intranasal route with
nanoparticles found effective through biological tissue for the
treatment of Parkinson’s disease. Here in we discussed various
approaches including ocular route and factors, which affects the BBB
permeability.
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