No abstract

Parkinson's disease (PD) is the only neurodegenerative disorder in which pharmacological intervention has resulted in a marked decrease in morbidity and a significant delay in mortality. The discovery of striatal dopamine deficiency as the neurochemical basis of PD in 1960 was a pivotal event that led to the era of levodopa therapy. Although levodopa produces dramatic improvements in patients' symptoms, it is also associated with adverse effects that can be disabling. Some of these are felt to be related to fluctuating levels of levodopa in the plasma and brain, and as a result, research has focused on drugs that can provide more continuous dopamine receptor stimulation. Dopamine agonists and catechol-O-methyl-transferase (COMT) inhibitors have been valuable adjuncts to levodopa, but until now levodopa has remained the cornerstone of therapy. Recent studies indicate that the newer dopamine agonists may be assuming greater importance in the control of symptoms. Other drugs, such as nicotinic acetylcholine receptor agonists, neurotrophic factors and adenosine receptor antagonists are under investigation. Efforts are being concentrated on understanding the causes and mechanisms involved in the death of dopaminergic neurones in the substantia nigra. Overactivity of the subthalamic nucleus and glutamate-mediated excitotoxicity might play key roles in the genesis of the disease. Therapeutic approaches aimed at correcting these abnormalities may lead to neuroprotective therapy that can inhibit or prevent the relentless progression of nigral neuronal loss. Well- controlled clinical trials using positron emission tomography (PET) and single photon emission computerised tomography (SPECT) will assist in assessing the putative neuroprotective properties attributed to various agents.

The study aims to develop enzymosomes as an emerging novel drug delivery system for site-specific action. Enzymosomes utilises the specific nature of an enzyme, which is binding to a specific substrate at a controlled rate and catalysing product production step. An enzyme is encapsulated by coupling covalently to the surface of liposomes/lipid vesicles to form enzymosomes. Enzymes links through acylation, direct conjugation, physical adsorption, encapsulation methods to prepare enzymosomes with targeted action. Such novel drug delivery systems prove effective drug release and concomitantly reduces undesirable side effects of conventional treatment methods and hence showcase improvement in the long-term therapy of the disease. They are a promising substitute to conventional treatment therapies of gout, antiplatelet activities etc. Enzymosomes are newly designed supramolecular vesicular delivery systems to be useful as a tool in pharmaceutics for the raising of drug targeting and physicochemical properties and hence bioavailability. It shows beneficial effects of drugs with a narrow precision because targeting of these drugs to their site of action improves the drugs overall pharmacodynamics and pharmacokinetic profile. It also minimizes alterations in the normal enzymatic activity, thus enhancing half-life and achieve enzyme activity on targeted sites such as cancerous cells.

Objective: To formulate and characterize midazolam loaded niosomal transdermal patches for overcoming the frequent dosing and lower bioavailability complications associated with conventional therapy. Methods:The loaded niosomal transdermal patches were prepared by thin film hydration method. The preliminary evaluation and characterization studies was conducted to find the optimised formulation. The in vitro release and ex-vivo permeation studies were investigated. The histopathological studies and stability studies were also assessed. Results:The midazolam loaded niosomal transdermal patches of vesicle size and zeta potential 116.1±84.46 d. nm and 8.56±1.2 mV respectively was formulated. The characterizations of both niosome and niosomal transdermal patches were found to be within the acceptable limits. The in vitro drug release showed an initial burst release followed by sustained release for both optimised niosomal formulation N5 and optimised niosomal transdermal patch formulation NT5with a maximum activity at 97.3±0.35% and 98.9±0.20% respectively. The ex vivo permeation studies of niosomal transdermal patch NT5 was performed which showed a higher permeability than control solution with a flux value of 0.151. The histopathological studies of the optimised formulation showed no detectable lesions upon skin surface and irritations. The stability studies showed that patches were stable over 90 d in different atmospheric conditions. Conclusion:The midazolam loaded niosomal transdermal patch was found to be a promising nano drug delivery alternative which showed better entrapment, release with permeation profile for the daily management of epilepsy with decreased dosing frequency. I In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f A Ap pp pl li ie ed d P Ph ha ar rm ma ac ce eu ut ti ic cs s