Design of quetiapine fumarate loaded polyethylene glycol decorated graphene oxide nanosheets: Invitro-exvivo characterization.

Quetiapine Fumarate (QF) is an atypical antipsychotic with poor oral bioavailability (9%) due to its low permeability and pH-dependent solubility. Therefore, this study aims to design QF-loaded polyethylene glycol (PEG) functionalized graphene oxide nanosheets (GON) for nasal delivery of QF. In brief, GO was synthesized using a modified Hummers process, followed by ultra-sonication to produce GON. Subsequently, PEG-functionalized GON was prepared using carbodiimide chemistry (PEG-GON). QF was then decorated onto the cage of PEG-GON using the π-π stacking phenomenon (QF@PEG-GON). The QF@PEG-GON nanocomposite underwent several spectral characterizations, in vitro drug release, mucoadhesion study, ex vivo diffusion study, etc. The surface morphology of QF@PEG-GON nanocomposite validates the cracked nature of the nanocomposite, whereas the diffractograms and thermogram of nanocomposite confirm the conversion of QF into an amorphous form with uniform distribution in PEG-GON. Moreover, an ex vivo study of PEG-GON demonstrates superior mucoadhesion capacity due to its surface functional groups and hydrophilicity. The percent drug loading content and percent entrapment efficiency of the nanocomposite were found to be 9.2±0.62% and 92.3±1.02%, respectively. The developed nanocomposite exhibited 43.82±1.65% drug release within 24h, with the Korsemeyer-Peppas model providing the best-fit release kinetics (R2: 0.8614). Here, the interlayer spacing of PEG-GON prevented prompt diffusion of the buffer, leading to a delayed release pattern. In conclusion, the anticipated QF@PEG-GON nanocomposite shows promise as a nanocarrier platform for nasal delivery of QF.

Recent advancement in discovery and development of natural product combretastatin-inspired anticancer agents.

The natural stilbenoids combretastatin A-4 (CA4) and combretastatin A-1 (CA1) are potent antitubulin agents demonstrating antimitotic activity as well as tumor vascular disruption property. Due to structural simplicity and potent cytotoxicity of CA4 and CA1, they are considered as promising leads for the development of potent anticancer agents. In fact, scientific fraternity is motivated to synthesize several derivatives of CA4 and CA1 as novel therapeutic agents. In the literature, several studies have been carried out to evaluate the medicinal chemistry, pharmacology and structure-activity relationships (SAR) of a variety of modified combretastatin derivatives. The present report aimed at comprehensively revising the recent advancements (2006-2014) in the medicinal chemistry and SAR of diversified combretastatin analogues. The published data concerning new combretastatin A-4 analogues as antimitotic anticancer agents are presented and SAR is reviewed and discussed.

Animal models for Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease with major impacts on patients' lives and on society as a whole. It is one of the most common neurodegenerative diseases in the world, second only to Alzheimer's disease. Low levels of production of dopamine (DA) are associated with PD. This is caused by a progressive loss of neurons in the midbrain's substantia nigra, resulting in changes in neural conduction within the nigrostriatum. Research into PD has been going on since 1960, still there is no cure although the symptoms can be effectively controlled and the severity of the affliction can be reduced. The main obstacle in the development of neuroprotective therapy is a limited understanding of the key molecular events that provoke neurodegeneration. A misfolding of proteins and dysfunction of the ubiquitin-proteasome pathway are the critical factors in the pathogenesis of PD. Neurotoxic models (particularly 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine) have been very useful in elucidating the molecular cascade of cell death in dopaminergic neurons. They are also of use in efforts to limit the progression of the disease and to prevent the long-term functional and pathological outcome in PD. The establishment of animal and cellular models of mutations in LRRK2 and α-synuclein, and mutations in parkin, DJ-1 and PINK1, has been of use in elucidating the molecular mechanisms of this disorder, and research using these models is providing new ideas about the pathogenesis of PD. Several researchers are synthesizing and screening novel derivatives for their antiparkinsonian potential using different animal models. In this work we describe different animal models used in assessing the antiparkinson activity of novel therapeutic treatments.

Nanoarchitectonics in cancer therapy and imaging diagnosis.

Nanoarchitectonics has gained remarkable importance due to the fabrication of various recent nanostructures with the capability of being used in biomedical science, particularly in cancer diagnosis and treatment. These nanosized structures possess unique physical and optical properties that can be exploited for cancer therapeutics, and so nanoarchitectonics is popularly known as nanomedicine. The goal of this review is to discuss the latest findings in nanostructures research including nanocrystals, nanotubes, nanoshells, nanopillars, nanoballs, nanoflowers, nanorods, nanocontainers, nanobelts, nanocages, nanodiscs, nanodots, nanoprisms, nanoplates, nanorings, nanocubes, nanobranches, nanospheres, nanorattles, nanostars, nanotrees, nanowires, nanowalls, nanodiamonds, nanosheets, layered nanostructures, quantum dots, mesoporous nanostructures etc. in the field of cancer therapy and imaging. This review further highlights brief information about use of radionuclide in cancer. Lastly, different nanoformulations that are available in the market or are under clinical trials for cancer therapy and imaging are discussed.

A comprehensive review on synthesis and designing aspects of coumarin derivatives as monoamine oxidase inhibitors for depression and Alzheimer's disease.

Monoamine oxidase (MAO) enzyme inhibition is a crucial target for the management of depression and Alzheimer disease and inhibitors of MAO are the most important drugs for their management. Coumarins are a large family of compounds, of natural and synthetic origin, that exhibit a variety of pharmacological activities, including MAO inhibition. The current review highlights the design and synthetic methods of coumarin derivatives as well as coumarins obtained from plant source as MAO inhibitors for treatment of depression and Alzheimer disease with salient finding related to structure-activity relationship. The aim of present review is to find out natural as well as synthetic coumarins as MAO inhibitors.

Geochemical studies of fluoride and other water quality parameters of ground water in Dhule region Maharashtra, India.

This study has been carried out to find out the water pollutants and to test the suitability of water for drinking and irrigation purposes in Dhule and surrounding areas in Maharashtra State in India. The analysis was carried out for the parameters pH, DO (dissolved oxygen), BOD (biological oxygen demand), Cl-, NO3-, F-, S(2)-, total alkalinity, total solid, total dissolved solids (TDS), total suspended solids (TSS), total hardness, calcium, magnesium, carbonate and noncarbonate hardness, and concentrations of calcium and magnesium. These parameters were compared against the standards laid down by World Health Organization (WHO) and Indian Council of Medical Research (ICMR) for drinking water quality. High levels of NO(3)-, Cl-, F-, S(2)-, total solid, TDS, TSS, total hardness, magnesium and calcium have been found in the collected samples. From these observations, it has been found that fluoride is present as per the permissible limit (WHO 2003) in some of the villages studied, but both fluoride and nitrate levels are unacceptable in drinking water samples taken from several villages in Dhule. This is a serious problem and, therefore, requires immediate attention. Excess of theses impurities in water causes many diseases in plants and animals. This study has been carried out to find out the water pollutants and to test the suitability of water for drinking and irrigation purposes in Dhule and surrounding areas in Maharashtra.