BRAIN DRUG DELIVERY OF NANOPARTICLES BY NASAL ROUTE FOR THE TREATMENT OF DEPRESSION

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ABOUT AUTHORS:
Rakhi Choudhary*, Lakshmi Goswami , Preeti Kothiyal
Shri Guru Ram Rai Institute of Technology & Science P.O. Box - 80, Patel Nagar,
Dehradun 248001, Uttarakhand , India
rakhichaudhary211@gmail.com

ABSTRACT
Major depression is a mood disorder characterized by a sense of inadequacy, despondency, decreased activity, pessimism and sadness where these symptoms severely disrupt and adversely affect the person’s life, sometimes to such an extent that suicide is attempted or results. Various Strategies are used for the treatment of depression by giving drug by various routes. Nasal drug delivery is the best route for treatment of CNS disorder as it is the direct route for the delivery of drug.

REFERENCE ID: PHARMATUTOR-ART-2011

INTRODUCTION:
As estimated by WHO, depression shall become the second largest illness in terms of morbidity by another decade in the world, already one out of every five women, and twelve men have depression. Not just adults, but two percent of school children, and five percent of teenagers also suffer from depression, and these mostly go unidentified. Depression has been the commonest reason why people come to a psychiatrist, although the common man's perception is that all psychological problems are depression[1,2].

TYPES OF DEPRESSION
Depressive illness comes in different forms, just as many other illnesses:

* Major depression is manifested by a combination of symptoms that interfere with the ability to work, sleep, eat and enjoy once pleasurable activities. These disabling episodes of depression can occur once, twice or several times in a lifetime.

* Dysthymia, a less severe type of depression, involves long-term, chronic symptoms that do not disable, but keep you from functioning at “full steam” or from feeling good. Sometimes people with dysthymia also experience major depressive episodes.

* Manic-depressiveor bipolar is not nearly as prevalent as other forms of depressive illnesses. It involves cycles of depression and elation or mania. Sometimes the mood switches are dramatic and rapid, but most often they are gradual. When in the depressed cycle, one can have any or all other the symptoms of a depressive illness. When in the manic cycle, any or all symptoms listed under mania may be experienced. Mania often affects thinking, judgment, and social behaviour in ways that may cause serious problems and embarrassment[3,4].

Depression is an illness with a combination of associated symptoms of which the dominant one is a depressed state of mind accompanied by feelings of sadness and/or anxiety and/or irritability. It is a lengthy illness (i.e. one lasting at least two weeks).

Depression affects the way we function in various ways:

* Biological functions: a disturbed sleep pattern; increased or reduced appetite; reduced libido and energy;

* Motivational functions: a reduced interest in others, in leisure activities, in daily life, in doing activities or reduced pleasure in doing them, a feeling of uselessness and incompetence and in the worst cases suicidal feelings;

* Cognitive functions: loss of self-esteem, inability to take decisions, pessimism and despair, reduced powers of concentration or attention; generally negative psychological attitudes;

* Behavioural functions: slower cerebral or motor functions, or, conversely, an agitated state; reduced frequency of active and productive behaviour, increased frequency of passive and unproductive behaviour.

Sleep alterations and depression:
Sleep alterations is associated with affective disorders. The most common complaint of sleep disturbance in patients with major depression is insomnia. Difficulty falling asleep, frequent nocturnal awakenings, early morning awakening, non sleep, decreased total sleep, and disturbing dreams with more negative emotional content are often reported[5].

Objective sleep disturbances as assessed by polysomnographic recordings, confirm subjective experience in the majority of depressed patients. However, manifestation of most sleep abnormalities only occurs when depressive symptoms are present.

Usually, sleep alterations in depression are grouped into three general categories:-
Sleep continuity disturbances- Prolonged sleep latency, frequent arousals during sleep and early awakening in the morning. The sleep is more fragmentized which results in decreased sleep efficiency and reduced amount of sleep.

Slow wave sleep(SWS changes)- SWS processes depression as indicated by a reduction of the SWS.

REM sleep changes- A reduced REM sleep latency (period of time from sleep onset to the first REM sleep period, prolonged duration of the first REM sleep episode, increased percentage of REM sleep and more frequent eye movements (increased REM sleep density during REM sleep are often reported in depression[6,7].

Depression usually leads to
-   Difficulty getting to sleep
-   Poor quality sleep
-   Fewer Hours of sleep
-   More awakenings during the night
-   In severe cases, waking very early in the morning and being unable to get back to sleep
-   Daytime tiredness

Advances in understanding of the cell biology of the BBB have opened new avenues and possibilities for improved drug delivery to the Central Nervous System (CNS). The blood brain barrier transport mechanism is shown in fig. 1

Various strategies are available for the treatment of depression[8].

Strategies for brain delivery of drug:

Invasive Strategies
BBB disruption
Intracerebral implants

Physiological Strategies
Pseudo nutrients
Ligand binding proteins
Chimeric peptides

Pharmacological Strategies
Prodrug based brain targeting
Nanoparticles
Redox chemical delivery system
Liposomes.
Nanoconjugates
Vector mediated delivery


One of the most commonly used pharmacological strategies for the treatment of various neurological disorders like depression is nanoparticles.

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