Effects of Current Psychotropic Drugs on Inflammation and Immune System.

The immune system and inflammation are involved in the pathological progression of various psychiatric disorders such as depression or major depressive disorder (MDD), generalized anxiety disorder (GAD) or anxiety, schizophrenia, Alzheimer's disease (AD), and Huntington's disease. It is observed that levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and other markers are highly increased in the abovementioned disorders. The inflammation and immune component also lead to enhance the oxidative stress. The oxidative stress and increased production of reactive oxygen species (ROS) are considered as important factors that are involved in pathological progression of psychiatric disorders. Increase production of ROS is associated with excessive inflammation followed by cell necrosis and death. The psychotropic drugs are mainly work through modulations of neurotransmitter system. However, it is evident that inflammation and immune modulation are also having important role in the progression of psychiatric disorders. Rationale of the use of current psychotropic drugs is modulation of immune system by them. However, the effects of psychotropic drugs on the immune system and how these might contribute to their efficacy remain largely unclear. The drugs may act through modification of inflammation and related markers. The main purpose of this book chapter is to address the role of current psychotropic drugs on inflammation and immune system. Moreover, it will also address the role of inflammation in the progression of psychiatric disorders.

Significant delivery of tacrine into the brain using magnetic chitosan microparticles for treating Alzheimer's disease.

Alzheimer's disease (AD) is a progressive degenerative disorder of the brain characterized by a slow, progressive decline in cognitive function and behavior. As the disease advances, persons have a tough time with daily tasks like using the phone, cooking, handling money or driving the car. AD affects 15 million people worldwide and it has been estimated that AD affects 4.5 million Americans. Tacrine is a reversible cholinesterase inhibitor used for treating mild to moderate AD. In the present study, an attempt was made to target the anti-Alzheimer's drug tacrine in the brain by using magnetic chitosan microparticles. The magnetic chitosan microparticles were prepared by emulsion cross-linking. The formulated microparticles were characterized for process yield, drug loading capacity, particle size, in vitro release, release kinetics and magnetite content. The particle size was analyzed by scanning electron microscope. The magnetite content of the microparticles was determined by atomic absorption spectroscopy. For animal testing, the microparticles were injected intravenously after keeping a suitable magnet at the target region. The concentrations of tacrine at the target and non-target organs were analyzed by HPLC. The magnetic chitosan microparticles significantly increased the concentration of tacrine in the brain in comparison with the free drug.

Poly(n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer's disease.

Alzheimer's disease is a progressive and fatal neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living, and a variety of neuropsychiatric symptoms and behavioral disturbances. Alzheimer's disease affects 15 million people worldwide and it has been estimated that Alzheimer's disease affects 4.5 million Americans. Rivastigmine is a reversible cholinesterase inhibitor used for the treatment of Alzheimer's disease. Central nervous system drug efficacy depends upon the ability of a drug to cross the blood-brain barrier and reach therapeutic concentrations in brain following systemic administration. The clinical failures of most of the potentially effective therapeutics to treat the central nervous system disorders are often not due to a lack of drug potency but rather shortcomings in the method by which the drug is delivered. Hence, considering the importance of treating Alzheimer's disease, we made an attempt to target the anti-Alzheimer's drug rivastigmine in the brain by using poly(n-butylcyanoacrylate) nanoparticles. The drug was administered as a free drug, bound to nanoparticles and also bound to nanoparticles coated with polysorbate 80. In the brain a significant increase in rivastigmine uptake was observed in the case of poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 compared to the free drug. In conclusion that the present study demonstrates that the brain concentration of intravenously injected rivastigmine can be enhanced over 3.82 fold by binding to poly(n-butylcyanoacrylate) nanoparticles coated with 1% nonionic surfactant polysorbate 80.

Targeted delivery of tacrine into the brain with polysorbate 80-coated poly(n-butylcyanoacrylate) nanoparticles.

The purpose of the present study was to investigate the possibility of targeting an anti-Alzheimer's drug tacrine in the brain using polymeric nanoparticles. Rats obtained 1mg/kg of tacrine by intravenous injection in the form of three preparations: (1) a simple solution in phosphate buffered saline, (2) bound to poly(n-butylcyanoacrylate) nanoparticles, and (3) bound to poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 (Tween 80). After 1h of post injection the rats were killed by decapitation and tacrine concentration in brain, liver, lungs, spleen and kidneys was analyzed by HPLC. A higher concentration of drug tacrine was observed in liver, spleen and lungs with the nanoparticles in comparison to the free drug. The accumulation of drug tacrine in the liver and spleen was reduced, when nanoparticles were coated with 1% polysorbate 80. In the brain a significant increase in tacrine concentration was observed in the case of poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 compared to the uncoated nanoparticles and the free drug. In conclusion, the present study demonstrates that the brain concentration of intravenously injected tacrine can be enhanced by binding to poly(n-butylcyanoacrylate) nanoparticles, coated with 1% the nonionic surfactant polysorbate 80.