Alzheimer's disease is a growing concern in the modern world. As the currently available medications are not very promising, there is an increased need for the fabrication of newer drugs. Curcumin is a plant derived compound which has potential activities beneficial for the treatment of Alzheimer's disease. Anti-amyloid activity and anti-oxidant activity of curcumin is highly beneficial for the treatment of Alzheimer's disease. The insolubility of curcumin in water restricts its use to a great extend, which can be overcome by the synthesis of curcumin nanoparticles. In our work, we have successfully synthesized water-soluble PLGA coated- curcumin nanoparticles and characterized it using different techniques. As drug targeting to diseases of cerebral origin are difficult due to the stringency of blood-brain barrier, we have coupled the nanoparticle with Tet-1 peptide, which has the affinity to neurons and possess retrograde transportation properties. Our results suggest that curcumin encapsulated-PLGA nanoparticles are able to destroy amyloid aggregates, exhibit anti-oxidative property and are non-cytotoxic. The encapsulation of the curcumin in PLGA does not destroy its inherent properties and so, the PLGA-curcumin nanoparticles can be used as a drug with multiple functions in treating Alzheimer's disease proving it to be a potential therapeutic tool against this dreaded disease.

Nanomedicine utilizes engineered nanodevices and nanostructures for monitoring, repair, construction and control of human biological systems at the molecular level. In this study, we investigated the feasibility and potential of zein nanofiber as a delivery vehicle for curcumin in biomedical applications. By optimizing the electrospinning parameters, ultrafine zein fluorescence nanofibers containing curcumin were developed with interconnected fibrous networks. We found that these nanofibers show an increase in fluorescence due to the incorporation of curcumin. The morphology and material properties of the resulting multifunctional nanofiber including the surface area were examined by a field emission-scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and confocal microscopy. The surface area and pore size were characterized by N(2) adsorption-desorption isotherm. SEM and fluorescence images showed that the uniform fibers with smooth surface had an average diameter of about 310 nm. An in vitro degradation study showed significant morphological changes. The in vitro evaluations suggested that the curcumin incorporated zein nanofibers showed sustained release of curcumin and maintained its free radical scavenging ability. It provides an attractive structure for the attachment and growth of fibroblast as cell culture surfaces. The results demonstrate that the curcumin loaded zein nanofiber could be a good candidate for soft tissue engineering scaffolds and has the potential for further applications in drug delivery system.

The transmembrane P-glycoprotein that functions as a drug-efflux transporter coded by ATP-binding cassette, subfamily B, member 1/Multidrug Resistance 1 (ABCB1/MDR1) gene is considered relevant to drug absorption and elimination, with access to the central nervous system. Effects of three ABCB1 single nucleotide polymorphisms (SNPs) in genotypic and haplotypic combination have been evaluated in a south Indian population for risk of pediatric medically refractory epilepsy. The study included age and sex matched medically refractory (N=113) cases and drug responsive epilepsy patients (N=129) as controls, belonging to the same ethnic population recruited from a tertiary referral centre, of Karnataka, Southern India. The genotype frequencies of SNPs c.1236C>T, c.2677G>T/A, and c.3435C>T were determined from genomic DNA of the cases and controls by PCR- RFLP and confirmatory DNA sequencing. 256 normal population samples of the same ethnicity were genotyped for the three loci to check for population stratification. Results indicate that there was no statistically significant difference between allele and genotype frequencies of refractory and drug responsive epilepsy patients. The predicted haplotype frequencies of the three polymorphisms did not show significant difference between cases and controls. The results confirm earlier observations on absence of association of ABCB1 polymorphisms with medically refractory epilepsy.

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Cancer is one of the leading causes of death in most parts of the world and is a very serious cause of concern particularly in developing countries. In this work, we prepared and evaluated the aptamer-labeled paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Apt-PTX-PLGA NPs) which can ameliorate drug bioavailability and enable accurate drug targeting to cancer cells with controlled drug release for cancer therapy. Paclitaxel-loaded PLGA nanoparticles (PTX-PLGA NPs) were formulated by a single-emulsion/solvent evaporation method and were further surface-functionalized with a chemical cross-linker bis(sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. The prepared nanoparticles were characterized by atomic force microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Cytotoxicity studies were carried out using normal human mammary epithelial cells (HMEC cells) and human glial cancer cells (GI-1 cells) by methylthiazolyldiphenyl-tetrazolium bromide assay and Alamar blue assay, which confirmed that PTX-PLGA NPs with aptamer conjugation (Apt-PTX-PLGA NPs) were comparatively non-toxic to HMEC cells while toxic to GI-1 cancer cells. Cellular uptake of PTX-PLGA NPs with and without aptamer conjugation was studied using GI-1 cells and monitored by confocal microscopy and phase contrast microscopy. Our studies demonstrated significant internalization and retention of nanoparticles inside the cells, inducing apoptosis. The preferential accumulation of PTX-PLGA NPs within the cancer cells were also confirmed by flow cytometry-based uptake studies. The results indicated that Apt-PTX-PLGA NPs could be a promising targeted therapeutic delivery vehicle for cancer treatment.

The study suggests that a priori knowledge of ABCB1 genotypes can provide a significant input into evaluating the patient's response to medication, and minimizing redundant dosing and refractoriness.

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